Difference between revisions of "Paper - The development of the human vagina"

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THE DEVELOPMENT OF THE HUMAN VAGINA
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{{Ref-Bulmer1957}}
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{| class="wikitable mw-collapsible mw-collapsed"
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! Online Editor Note 
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| [[File:Mark_Hill.jpg|90px|left]] This historic 1957 paper by Bulmer is an early description of female vagina development. Current research suggests that Bulmer's description is more correct and that Koff's (1937).
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See also {{Ref-Koff1933}}
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'''Modern Notes:''' [[Vagina Development]] | [[Genital System Development]] | [[Fetal Development]]
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{{Genital Links}}
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|}
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{{Historic Disclaimer}}
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=The Development Of The Human Vagina=
 +
 
 +
By D. Bulmer
  
BY D. BULMER
 
 
Anatomy Department, University of Aberdeen
 
Anatomy Department, University of Aberdeen
  
The literature on the development of the human vagina is already so abundant that
+
==Introduction==
this further contribution is made only with some trepidation. However, the findings
+
The literature on the development of the human vagina is already so abundant that this further contribution is made only with some trepidation. However, the findings which form the substance of this paper seem of sufficient significance to be recorded, since they clearly demonstrate a method of vaginal development which has not so far been generally accepted in this country. The material studied, while not always forming as complete a series as might be wished, has in most cases been in excellent condition for detailed histological examination, and it is possible that the previous confusions and disagreements on this subject were largely due to deficiencies in the material available to earlier workers.
which form the substance of this paper seem of sufficient significance to be recorded,
+
 
since they clearly demonstrate a method of vaginal development which has not so
+
 
far been generally accepted in this country. The material studied, while not always
+
Bloomfield & Frazer (1927) pointed out that the descriptions of vaginal development in the literature could be divided into three main groups, depending on the structures which their authors believed to take part in the formation of the vagina, and it will be convenient to employ this classification here.
forming as complete a series as might be wished, has in most cases been in excellent
+
 
condition for detailed histological examination, and it is possible that the previous
+
 
confusions and disagreements on this subject were largely due to deficiencies in the
+
In the first group are those accounts which have attributed the origin of the entire vagina to the lower end of the Mullerian utero-vaginal canal. This opinion first gained general acceptance from the demonstration by Thiersch and others, work which is well summarized by Banks (1864), of the fusion of the Miillerian ducts in the genital cord, and in this century has been supported by Felix (1912), Bloomfield & Frazer (1927), Hunter (1930) and von Lippmann (1939). It may be regarded as the ‘ classical’ account of vaginal development, and was for many years the standard textbook description.
material available to earlier workers.
+
 
 +
 
 +
The second group consists of those descriptions which supposed that the vaginal epithelium was formed in part (Tourneux & Legay, 1884; Mijsberg, 1924) or in whole (Hart, 1896, 1901 and 1911; Kempermann, 1931) from the lower ends of the Wolffian ducts.
 +
 
 +
 
 +
The third group includes the accounts of all those workers who believed that the epithelium of the urogenital sinus made a contribution to the vagina. Before the time of Thiersch it was accepted that the entire vagina was derived from the sinus (Muller, 1830; Rathke, 1832; Valentin, 1835), but this opinion was discarded when the fusion of the Miillerian ducts became known. Retterer (1891), however, suggested that while most of the vagina was formed from the utero-vaginal canal a short lower segment arose by the splitting of the upper part of the sinus into dorsal and ventral channels, and this view was later supported by Bolk (1907). Koff (1933), whose work is recognized by most current British and American textbooks, believed that the lower one-fifth of the vagina was derived from the sinus by the growth of paired epithelial ‘sino-vaginal bulbs’ from the dorsal sinus wall, these bulbs fusing together to form a lower vaginal segment. On the other hand, Spuler (1930), Vilas (1932), Kempermann (1935) and Meyer (1934-38) believed that a proliferation of cells from the dorsal wall of the sinus gave rise to the epithelial lining of the entire vagina, displacing the epithelium of the utero-vaginal canal as far as the cervix. This opinion has recently been supported by Politzer (1955), and Zuckerman (1940) showed that there was a considerable body of endocrinological evidence in its favour.
 +
 
 +
==Material==
 +
 
 +
The material consists of thirteen embryos and foetuses, ranging from 28 to 375 mm. crown—rump length, and an infant of 1 month. The majority of the specimens were already sectioned and stained with haematoxylin and eosin, alternately with haematoxylin and eosin and a trichrome stain, or by the de Castro method of silver impregnation. The remainder were sectioned at 6-10 /1., either transversely or coronally, and the sections stained mainly with haematoxylin and eosin or a trichrome stain. With some of the larger specimens slides were also stained with Best’s ammoniacal carmine and by the periodic acid-Schiff technique (Gomori, 1952)
  
Bloomfield & Frazer (1927) pointed out that the descriptions of vaginal develop-
+
==28 mm Embryo==
ment in the literature could be divided into three main groups, depending on the
 
structures which their authors believed to take part in the formation of the vagina,
 
and it will be convenient to employ this classification here.
 
  
In the first group are those accounts which have attributed the origin of the
 
entire vagina to the lower end of the Miillerian utero-vaginal canal. This opinion first
 
gained general acceptance from the demonstration by Thiersch and others, work
 
which is well summarized by Banks (1864), of the fusion of the Miillerian ducts in
 
the genital cord, and in this century has been supported by Felix (1912), Bloomfield
 
& Frazer (1927), Hunter (1930) and von Lippmann (1939). It may be regarded as
 
the ‘ classical’ account of vaginal development, and was for many years the standard
 
textbook description.
 
  
The second group consists of those descriptions which supposed that the vaginal
+
In the lower part of the genital cord the Miillerian ducts are in apposition with each other, their medial walls forming a septum between the two lumina. They are lined by a closely packed columnar epithelium and lie between the two Wolffian ducts, rather larger structures with a cubical epithelium. The caudal ends of the Miillerian ducts do not quite reach the dorsal wall of the sinus, remaining separated from the Miillerian tubercle by a small mass of mesoderm, but on either side they are in close contact with the lowerends of the Wolffian ducts (Pl. 1, fig. 1).
epithelium was formed in part (Tourneux & Legay, 1884; Mijsberg, 1924) or in
 
whole (Hart, 1896, 1901 and 1911; Kempermann, 1931) from the lower ends of the
 
Wolffian ducts. I
 
  
The third group includes the accounts of all those workers who believed that the
 
epithelium of the urogenital sinus made a contribution to the vagina. Before the
 
time of Thiersch it was accepted that the entire vagina was derived from the sinus
 
(Muller, 1830; Rathke, 1832; Valentin, 1835), but this opinion was discarded when
 
the fusion of the Miillerian ducts became known. Retterer (1891), however,
 
suggested that while most of the vagina was formed from the utero-vaginal canal
 
a short lower segment arose by the splitting of the upper part of the sinus into
 
dorsal and ventral channels, and this view was later supported by Bolk (1907).
 
Koff (1933), whose work is recognized by most current British and American
 
textbooks, believed that the lower one-fifth of the vagina was derived from the
 
sinus by the growth of paired epithelial ‘sino-vaginal bulbs’ from the dorsal sinus
 
wall, these bulbs fusing together to form a lower vaginal segment. On the other
 
hand, Spuler (1930), Vilas (1932), Kempermann (1935) and Meyer (1934-38)
 
The development of the human vagina 491
 
  
believed that a proliferation of cells from the dorsal wall of the sinus gave rise to the
+
Most of the pars pelvina of the sinus is lined by an epithelium consisting of three or four layers of small, darkly staining cells with closely arranged nuclei, but in the region of the Miillerian tubercle the epithelium of the dorsal sinus wall is differentiated into a thin basal layer of deeply staining cells overlain by’ one to three layers of larger and very pale staining cells with relatively smaller nuclei. At the Wolffian openings, on either side of the Miillerian tubercle, these pale cells seem to be compressed together, and they extend backwards for a short distance into the lower ends of the Wolffian ducts themselves.
epithelial lining of the entire vagina, displacing the epithelium of the utero-vaginal
 
canal as far as the cervix. This opinion has recently been supported by Politzer
 
(1955), and Zuckerman (1940) showed that there was a considerable body of endo-
 
crinological evidence in its favour.
 
  
MATERIAL
+
==42 mm Foetus==
  
The material consists of thirteen embryos and foetuses, ranging from 28 to 375 mm.
+
The lower portions of the Miillerian ducts are completely fused together as the utero-vaginal canal and the caudal tip of the Miillerian epithelium forms a solid mass in contact with the dorsal wall of the sinus, though a small central mass of mesoderm interrupts this contact in the midline. On either side of the Miillerian tubercle the Wolffian ducts enter the sinus, and are now of about the same calibre as the utero-vaginal canal. The sinus epithelium presents the same features as in the 28 mm. specimen (Pl. 1, fig. 2).
crown—rump length, and an infant of 1 month. The majority of the specimens were
 
already sectioned and stained with haematoxylin and eosin, alternately with
 
haematoxylin and eosin and a trichrome stain, or by the de Castro method of silver
 
impregnation. The remainder were sectioned at 6-10 /1., either transversely or
 
coronally, and the sections stained mainly with haematoxylin and eosin or a tri-
 
chrome stain. With some of the larger specimens slides were also stained with
 
Best’s ammoniacal carmine and by the periodic acid-Schiff technique (Gomori,
 
  
1952)
+
==50 mm Foetus==
28 mm. embryo
 
  
In the lower part of the genital cord the Miillerian ducts are in apposition with
+
This specimen shows no significant developmental change, except that the sinus epithelium in the region of the Miillerian tubercle is now considerably thicker. This epithelium, divided into basal deeply staining and superficial pale-staining zones, will in future be referred to as the differentiated type of sinus epithelium. 492 D. Bulmer
each other, their medial walls forming a septum between the two lumina. They are
 
lined by a closely packed columnar epithelium and lie between the two Wolffian
 
ducts, rather larger structures with a cubical epithelium. The caudal ends of the
 
Miillerian ducts do not quite reach the dorsal wall of the sinus, remaining separated
 
from the Miillerian tubercle by a small mass of mesoderm, but on either side they
 
are in close contact with the lowerends of the Wolffian ducts (Pl. 1, fig. 1).
 
  
Most of the pars pelvina of the sinus is lined by an epithelium consisting of three
+
==65 mm Foetus==
or four layers of small, darkly staining cells with closely arranged nuclei, but in the
 
region of the Miillerian tubercle the epithelium of the dorsal sinus wall is differentiated
 
into a thin basal layer of deeply staining cells overlain by’ one to three layers of
 
larger and very pale staining cells with relatively smaller nuclei. At the Wolffian
 
openings, on either side of the Miillerian tubercle, these pale cells seem to be com-
 
pressed together, and they extend backwards for a short distance into the lower ends
 
of the Wolffian ducts themselves.
 
  
42 mm. foetus
+
The Mullerian utero-vaginal canal is a large structure, oval in cross-section and with its long axis lying transversely (Pl. 1, fig. 3). Throughout most of its extent it is lined by a closely packed columnar epithelium, but about 0-3 mm. above the caudal end the lining cells lose their columnar arrangement and form a thick stratified polygonal epithelium, which at the lowermost tip completely occludes the lumen. The Wolffian ducts are very small structures, lined by a cubical epithelium, and lie on either side of the utero-vaginal canal. There is a short segment where the Wolffian ducts have completely disappeared, just above their lower ends, but they reappear below this to join the dorsal wall of the sinus.
  
The lower portions of the Miillerian ducts are completely fused together as the
 
utero-vaginal canal and the caudal tip of the Miillerian epithelium forms a solid
 
mass in contact with the dorsal wall of the sinus, though a small central mass of
 
mesoderm interrupts this contact in the midline. On either side of the Miillerian
 
tubercle the Wolffian ducts enter the sinus, and are now of about the same calibre
 
as the utero-vaginal canal. The sinus epithelium presents the same features as in
 
the 28 mm. specimen (Pl. 1, fig. 2).
 
  
50 mm. foetus
+
The urogenital sinus shows a very significant advance in the region previously occupied by the Miillerian tubercle (Pl. 1, figs. 4, 5, 6). On either side the Wolffian ducts join ‘dorso-lateral projections’ of the sinus, solid epithelial structures which prevent the communication of the ducts with the sinus lumen and are in contact on their dorso-medial aspects with the solid mass of Miillerian epithelium at the caudal end of the utero-vaginal canal. More medially, the Miillerian epithelium is displaced dorsally by a proliferation of darkly staining cells from the dorsal sinus wall, between the bases of the two dorso-lateral projections (Pl. 1, fig. 4). The dorso-lateral projections are each formed by a central mass" of pale-staining cells, with small nuclei, surrounded by a thin basal layer of more darkly staining cells, and the cubical cell lining of the lower ends of the Wolffian ducts is applied to their dorsal aspects. Caudal and ventral to the proliferation of darkly staining cells from the dorsal sinus wall, the pale-staining cells extend forwards and medially to form a crest projecting into the dorsal aspect of the sinus lumen (Pl. 1, figs. 5, 6)—the structure identified by Kempermann (1931) as the Wolflsche Kamm. Apart from this differentiation in the region previously occupied by the Miillerian tubercle, the remainder of the pars pelvina is lined by a darkly staining stratified epithelium of six or seven layers of small cells.
  
This specimen shows no significant developmental change, except that the sinus
 
epithelium in the region of the Miillerian tubercle is now considerably thicker. This
 
epithelium, divided into basal deeply staining and superficial pale-staining zones,
 
will in future be referred to as the differentiated type of sinus epithelium.
 
492 D. Bulmer
 
  
65 mm. foetus
+
In this specimen, therefore, the sinus cells in the region which was previously lined by the differentiated type of epithelium form a proliferative zone, apparently composed of three elements. On either side are the dorso-lateral projections, associated with the Wolffian openings, while between them is a proliferation of darkly staining cells from the dorsal sinus wall.
  
The Miillerian utero-vaginal canal is a large structure, oval in cross-section and
+
==68 mm Foetus==
with its long axis lying transversely (Pl. 1, fig. 3). Throughout most of its extent it is
 
lined by a closely packed columnar epithelium, but about 0-3 mm. above the caudal
 
end the lining cells lose their columnar arrangement and form a thick stratified
 
polygonal epithelium, which at the lowermost tip completely occludes the lumen.
 
The Wolffian ducts are very small structures, lined by a cubical epithelium, and lie
 
on either side of the utero-vaginal canal. There is a short segment where the
 
Wolffian ducts have completely disappeared, just above their lower ends, but they
 
reappear below this to join the dorsal wall of the sinus.
 
  
The urogenital sinus shows a very significant advance in the region previously
+
This specimen is at only a slightly later developmental stage than the 65 mm. foetus, but several interesting differences may be noted. The Wolffian ducts are present throughout the whole of the genital cord as small, but easily recognizable structures. The occlusion of the lumen of the caudal portion of the utero-vaginal canal reaches further cranially than in the 65 mm. specimen, to a distance of about 0-3 mm. above the junction of Miillerian and sinus epithelia. A small mesodermal mass is enclosed in the root of ‘the proliferation of darkly staining cells from the dorsal wall of the sinus, splitting it into bilateral elements which meet each other behind the mesodermal mass and are there in contact with the caudal end of the Miillerian epithelium (Text-fig. la).  
occupied by the Miillerian tubercle (Pl. 1, figs. 4, 5, 6). On either side the Wolffian
 
ducts join ‘dorso-lateral projections’ of the sinus, solid epithelial structures which
 
prevent the communication of the ducts with the sinus lumen and are in contact on
 
their dorso-medial aspects with the solid mass of Miillerian epithelium at the caudal
 
end of the utero-vaginal canal. More medially, the Miillerian epithelium is displaced
 
dorsally by a proliferation of darkly staining cells from the dorsal sinus wall,
 
between the bases of the two dorso-lateral projections (Pl. 1, fig. 4). The dorso-
 
lateral projections are each formed by a central mass" of pale-staining cells, with
 
small nuclei, surrounded by a thin basal layer of more darkly staining cells, and the
 
cubical cell lining of the lower ends of the Wolffian ducts is applied to their dorsal
 
aspects. Caudal and ventral to the proliferation of darkly staining cells from the
 
dorsal sinus wall, the pale-staining cells extend forwards and medially to form a
 
crest projecting into the dorsal aspect of the sinus lumen (Pl. 1, figs. 5, 6)—the
 
structure identified by Kempermann (1931) as the Wolflsche Kamm. Apart from
 
this differentiation in the region previously occupied by the Miillerian tubercle, the
 
remainder of the pars pelvina is lined by a darkly staining stratified epithelium of
 
six or seven layers of small cells.
 
  
In this specimen, therefore, the sinus cells in the region which was previously
 
lined by the differentiated type of epithelium form a proliferative zone, apparently
 
composed of three elements. On either side are the dorso-lateral projections,
 
associated with the Wolffian openings, while between them is a proliferation of
 
darkly staining cells from the dorsal sinus wall.
 
  
68 mm. foetus
+
The most interesting feature is the appearance of a characteristic system of longitudinal folds in the sinus wall (Text-fig. 1), foreshadowed at the 65 mm. stage but now very much more distinct. It may be noted that there is a pronounced fold—termed the ‘ urethro-vaginal fold ’——demarcating from the rest of the sinus its cranial and dorsal portion which forms the zone of contact with the Miillerian tissue. The dorsal margins of the urethro-vaginal folds run from the dorsal wall of the sinus, below the dorso-lateral projections, to meet each other behind the lower end of the urethra, and limit the area, dorsal and cranial to them, which is occupied by the differentiated type of sinus epithelium. The pattern of the folds in the wall of the human sinus has been described previously by Mijsberg (1924) and Politzer (1952). They are indicated in the diagrams in Text-figs. 1-4, and a more detailed account has been given elsewhere (Bulmer, 1955).
  
This specimen is at only a slightly later developmental stage than the 65 mm.
 
foetus, but several interesting differences may be noted. The Wolffian ducts are
 
present throughout the whole of the genital cord as small, but easily recognizable
 
structures. The occlusion of the lumen of the caudal portion of the utero-vaginal
 
canal reaches further cranially than in the 65 mm. specimen, to a distance of about
 
0-3 mm. above the junction of Miillerian and sinus epithelia. A small mesodermal
 
mass is enclosed in the root of ‘the proliferation of darkly staining cells from the
 
dorsal wall of the sinus, splitting it into bilateral elements which meet each other
 
behind the mesodermal mass and are there in contact with the caudal end of the
 
Miillerian epithelium (Text-fig. la).
 
The development of the human vagina 493
 
  
The most interesting feature is the appearance of a characteristic system of
+
'''Text-fig. 1.''' 68 mm. foetus. The figure on the left is a graphic reconstruction (x 20) of a median sagittal section through the lower end of the utero-vaginal canal and the urogenital sinus. The figures on the right, a-g, are transverse sections at the levels indicated in the sagittal section. The dorsal aspect of the sections is towards the left. The Miillerian epithelium is shown by the solid black shading, and the sinus epithelium by the stippling. A small area of connective tissue, ct in fig. 1 a, interrupts the sinus proliferation in the midline. The folds of the sinus wall are indicated in the transverse sections, and their relative positions in the sagittal section are shown by the dotted lines. dl, dorso-lateral fold; md, median dorsal fold; l, lateral fold; vl, ventro-lateral fold; uv, urethro-lateral fold ; v, median ventral fold. The dorso-lateral sinus bay lies between the lateral and dorso-lateral folds (figs. 1 f, 1 g) or between the lateral and median dorsal folds (fig. 1e), and is joined at ba by the duct of Bartholin’s gland. The ventro-lateral bay is between the lateral and ventro-lateral folds. It will be noticed that the relief of the sinus wall compares very closely with that described by Mij sberg (1924) and Politzer (1952) at similar developmental stages.
longitudinal folds in the sinus wall (Text-fig. 1), foreshadowed at the 65 mm. stage
 
but now very much more distinct. It may be noted that there is a pronounced
 
fold—termed the ‘ urethro-vaginal fold ’——demarcating from the rest of the sinus its
 
cranial and dorsal portion which forms the zone of contact with the Miillerian tissue.
 
The dorsal margins of the urethro-vaginal folds run from the dorsal wall of the sinus,
 
below the dorso-lateral projections, to meet each other behind the lower end of the
 
urethra, and limit the area, dorsal and cranial to them, which is occupied by the
 
  
{UV
+
==14 week Foetus==
  
Text-fig. 1. 68 mm. foetus. The figure on the left is a graphic reconstruction (x 20) of a median
+
The dorso-lateral projections can be identified, similar in structure to those of the 65 mm. stage, and their dorso-medial aspects are in contact with the Miillerian epithelium. Between their bases is the mass of darkly staining cells proliferating from the dorsal wall of the sinus, ventral to the Miillerian epithelium and now more extensive than in the 65 mm. foetus. 494 D. Bulmer
sagittal section through the lower end of the utero-vaginal canal and the urogenital sinus.
 
The figures on the right, a-g, are transverse sections at the levels indicated in the sagittal
 
section. The dorsal aspect of the sections is towards the left. The Miillerian epithelium is
 
shown by the solid black shading, and the sinus epithelium by the stippling. A small area of
 
connective tissue, ct in fig. 1 a, interrupts the sinus proliferation in the midline. The folds of
 
the sinus wall are indicated in the transverse sections, and their relative positions in the
 
sagittal section are shown by the dotted lines. dl, dorso-lateral fold; md, median dorsal fold;
 
l, lateral fold; vl, ventro-lateral fold; uv, urethro-lateral fold ; v, median ventral fold. The
 
dorso-lateral sinus bay lies between the lateral and dorso-lateral folds (figs. 1 f, 1 g) or between
 
the lateral and median dorsal folds (fig. 1e), and is joined at ba by the duct of Bartholin’s
 
gland. The ventro-lateral bay is between the lateral and ventro-lateral folds. It will be
 
noticed that the relief of the sinus wall compares very closely with that described by Mij sberg
 
(1924) and Politzer (1952) at similar developmental stages.
 
  
differentiated type of sinus epithelium. The pattern of the folds in the wall of the
+
==94 mm Foetus==
human sinus has been described previously by Mijsberg (1924) and Politzer (1952).
 
They are indicated in the diagrams in Text-figs. 1-4, and a more detailed account
 
has been given elsewhere (Bulmer, 1955).
 
  
14 week foetus
+
There is a considerable increase in size of the sinus compared with the 68 mm. stage (Text-fig. 2), but the arrangement of the longitudinal folds remains essentially unchanged. The urethro-vaginal fold is a marked feature, accentuated by the enlargement of the sinus which lies dorsal and cranial to it (Text-fig. 2b). This enlargement is associated with a considerable thickening of the epithelium, which now consists of a basal zone of five or six layers of small, darkly staining cells, with relatively large nuclei, clearly demarcated from a superficial zone of three or four layers of larger, clear staining polygonal cells with relatively much smaller nuclei. There is a striking distinction between the two zones in the low-power view (Pl. 2, fig. 7), and this epithelium is markedly different from the much thinner, undifferentiated type of epithelium, of four or five layers of smaller, rather darkly staining cells, which lines the rest of the pars pelvina.
  
The dorso-lateral projections can be identified, similar in structure to those of
 
the 65 mm. stage, and their dorso-medial aspects are in contact with the Miillerian
 
epithelium. Between their bases is the mass of darkly staining cells proliferating
 
from the dorsal wall of the sinus, ventral to the Miillerian epithelium and now more
 
extensive than in the 65 mm. foetus.
 
494 D. Bulmer
 
  
94 mm. foetus
 
  
There is a considerable increase in size of the sinus compared with the 68 mm.
 
stage (Text-fig. 2), but the arrangement of the longitudinal folds remains essentially
 
unchanged. The urethro-vaginal fold is a marked feature, accentuated by the
 
enlargement of the sinus which lies dorsal and cranial to it (Text-fig. 2b). This
 
enlargement is associated with a considerable thickening of the epithelium, which
 
now consists of a basal zone of five or six layers of small, darkly staining cells, with
 
relatively large nuclei, clearly demarcated from a superficial zone of three or four
 
layers of larger, clear staining polygonal cells with relatively much smaller nuclei.
 
There is a striking distinction between the two zones in the low-power view (Pl. 2,
 
fig. 7), and this epithelium is markedly different from the much thinner, un-
 
differentiated type of epithelium, of four or five layers of smaller, rather darkly
 
staining cells, which lines the rest of the pars pelvina.
 
  
/2 ,
+
'''Text-fig. 2.''' 94 mm. foetus. Median sagittal section through the sinus and the lower end of the vagina, with the corresponding coronal sections ( x 13;). Shading and lettering as for Text-fig. 1. The dotted lines in the sagittal section indicate the relative positions of the folds in the upper part of the sinus wall. The coronal sections, a——i, are shown with their cranial ends (i.e. the ventral wall of the sinus) towards the top.
  
Text-fig. 2. 94 mm. foetus. Median sagittal section through the sinus and the lower end of the
 
vagina, with the corresponding coronal sections ( x 13;). Shading and lettering as for Text-
 
fig. 1. The dotted lines in the sagittal section indicate the relative positions of the folds in the
 
upper part of the sinus wall. The coronal sections, a——i, are shown with their cranial ends
 
(i.e. the ventral wall of the sinus) towards the top.
 
  
The enlargement of the sinus behind the urethro-vaginal folds also forms the root
+
The enlargement of the sinus behind the urethro-vaginal folds also forms the root of a short ‘sinus upgrowth’, projecting dorsally and cranially from the sinus to meet the caudal end of the Miillerian epithelium. The lower end of the sinus up- growth contains paired lumina, continuous with the sinus lumen, and the epithelium is of the same differentiated type as that of the sinus enlargement. Followed further cranially the lumina disappear, and the sinus upgrowth forms a solid crescentic mass of epithelium in which the basal and superficial zones are still distinct (Pl. 2, fig. 8), though the basal cells are not so prominent as they are more caudally. In addition, a small mass of darkly staining cells, the caudal end of the Miullerian tissue, is embedded in this cranial end of the sinus upgrowth.
of a short ‘sinus upgrowth’, projecting dorsally and cranially from the sinus to
 
meet the caudal end of the Miillerian epithelium. The lower end of the sinus up-
 
growth contains paired lumina, continuous with the sinus lumen, and the epithelium
 
is of the same differentiated type as that of the sinus enlargement. Followed further
 
cranially the lumina disappear, and the sinus upgrowth forms a solid crescentic mass
 
of epithelium in which the basal and superficial zones are still distinct (Pl. 2, fig. 8),
 
though the basal cells are not so prominent as they are more caudally. In addition,
 
a small mass of darkly staining cells, the caudal end of the Miillerian tissue, is
 
embedded in this cranial end of the sinus upgrowth.
 
  
As the vaginal mass is followed still further cranially the left side of the sinus
 
upgrowth is joined by a short persistent segment of the lower end of the left Wolffian
 
duct, and the Miillerian epithelium comes to occupy a gradually increasing area in
 
The development of the human vagina 495
 
  
the centre. Eventually, about 240 ,a above the root of the sinus upgrowth, the sinus
+
As the vaginal mass is followed still further cranially the left side of the sinus upgrowth is joined by a short persistent segment of the lower end of the left Wolffian duct, and the Miillerian epithelium comes to occupy a gradually increasing area in the centre. Eventually, about 240 ,a above the root of the sinus upgrowth, the sinus cells are completely replaced by the solid Miillerian epithelium, which is canalized a short distance above this as the lower end of the utero-vaginal canal. This part of the canal is lined by a three- or four-layered stratified polygonal epithelium, which extends cranially to meet the columnar cell lining of the upper part. The level of junction between these two types of Miillerian epithelium coincides with a fusiform swelling of the genital cord, corresponding with that identified by Koff (1933) as the site of the future cervix.
cells are completely replaced by the solid Miillerian epithelium, which is canalized
 
a short distance above this as the lower end of the utero-vaginal canal. This part
 
of the canal is lined by a three- or four-layered stratified polygonal epithelium,
 
which extends cranially to meet the columnar cell lining of the upper part. The
 
level of junction between these two types of Miillerian epithelium coincides with
 
a fusiform swelling of the genital cord, corresponding with that identified by Koff
 
(1933) as the site of the future cervix.
 
  
It can be appreciated that several changes have occurred to reach this stage of
 
development. The three components which formed the proliferation of the sinus
 
from the 65 mm. stage onwards—the two dorso-lateral projections and the darkly
 
staining cells between them—have apparently fused together to form a single mass
 
which extends dorsally and cranially as the sinus upgrowth. The lower ends of the
 
Wolflian ducts have disappeared except for a short persistent segment on the left
 
side, which, as might be expected, joins the side of the sinus upgrowth. In addition,
 
the ‘ vaginal ’ portion of the utero-vaginal canal, so far as this can be defined, is now
 
entirely lined by a stratified polygonal epithelium, presumably derived from the
 
original columnar Miillerian epithelium. One of the most interesting features,
 
however, is the differentiation of the sinus epithelium behind and above the urethro-
 
vaginal folds. A similar differentiation, though less marked, has been noted since
 
the 28 mm. stage, always confined to this particular region of the sinus, and it is
 
from this differentiated type of epithelium that the sinus upgrowth appears to
 
arise.
 
  
112 mm. foetus
+
It can be appreciated that several changes have occurred to reach this stage of development. The three components which formed the proliferation of the sinus from the 65 mm. stage onwards—the two dorso-lateral projections and the darkly staining cells between them—have apparently fused together to form a single mass which extends dorsally and cranially as the sinus upgrowth. The lower ends of the Wolflian ducts have disappeared except for a short persistent segment on the left side, which, as might be expected, joins the side of the sinus upgrowth. In addition, the ‘ vaginal ’ portion of the utero-vaginal canal, so far as this can be defined, is now entirely lined by a stratified polygonal epithelium, presumably derived from the original columnar Mullerian epithelium. One of the most interesting features, however, is the differentiation of the sinus epithelium behind and above the urethro-vaginal folds. A similar differentiation, though less marked, has been noted since the 28 mm. stage, always confined to this particular region of the sinus, and it is from this differentiated type of epithelium that the sinus upgrowth appears to arise.
  
The configuration of the urogenital sinus shows little change from the 94 mm.
+
==112 mm Foetus==
stage, though the pars phallica is now becoming more dorso-ventrally elongated,
 
The sinus upgrowth extends for about 570 ,a above the dorsal wall of the sinus, as
 
a transversely elongated epithelial plate, and its cranial end reaches up for a short
 
distance as tapering ‘wings ’ on either side of the lower end of the utero-vaginal
 
canal. Caudally it is continuous with the dorsal wall of the sinus, but its root is
 
split into two by a small mesodermal septum (Pl. 2, fig. 9). Dorsal to this septum
 
the two roots join each other to form the sinus upgrowth, while on its ventral
 
aspect they are continuous with the enlarged dorsal and cranial portion of the sinus
 
which lies above and behind the urethro-vaginal folds. This arrangement obviously
 
cannot have arisen from conditions such as have been described in the 94 mm.
 
foetus. Apparently, as in the 68 mm. specimen, a small mesodermal septum must
 
have divided the root of the sinus upgrowth at the time of its initial formation.
 
  
The epithelium of the sinus upgrowth stains rather more deeply than in the
+
The configuration of the urogenital sinus shows little change from the 94 mm. stage, though the pars phallica is now becoming more dorso-ventrally elongated, The sinus upgrowth extends for about 570 ,a above the dorsal wall of the sinus, as a transversely elongated epithelial plate, and its cranial end reaches up for a short distance as tapering ‘wings ’ on either side of the lower end of the utero-vaginal canal. Caudally it is continuous with the dorsal wall of the sinus, but its root is split into two by a small mesodermal septum (Pl. 2, fig. 9). Dorsal to this septum the two roots join each other to form the sinus upgrowth, while on its ventral aspect they are continuous with the enlarged dorsal and cranial portion of the sinus which lies above and behind the urethro-vaginal folds. This arrangement obviously cannot have arisen from conditions such as have been described in the 94 mm. foetus. Apparently, as in the 68 mm. specimen, a small mesodermal septum must have divided the root of the sinus upgrowth at the time of its initial formation.
94 mm. foetus, but the basal and superficial zones can be readily recognized and it
 
can be distinguished from the Miillerian epithelium with which it is in contact (Pl. 2,
 
fig. 10). At the caudal end of the upgrowth, and in the enlargement of the dorsal
 
portion of the sinus from which it arises, the epithelium is of the same differentiated
 
type, but here the pale-staining cells are much larger and more prominent than they
 
are further cranially, their cytoplasm eosinophilic and their nuclei very small (Pl. 2,
 
fig. 9). The remainder of the pars pelvina is still lined by the same undifferentiated
 
type of epithelium as in the earlier stages.
 
496 D. Bulmer
 
  
The lower part of the utero-vaginal canal is lined by a stratified polygonal
 
epithelium, and the first sign of the differentiation of the surrounding mesoderm
 
which marks the position of the future external os (Bulmer, 1955) indicates that this
 
epithelium lines the entire ‘vaginal ’ portion of the canal, the uterine segment
 
retaining its original columnar epithelium.
 
  
16% week foetus
+
The epithelium of the sinus upgrowth stains rather more deeply than in the 94 mm. foetus, but the basal and superficial zones can be readily recognized and it can be distinguished from the Miillerian epithelium with which it is in contact (Pl. 2, fig. 10). At the caudal end of the upgrowth, and in the enlargement of the dorsal portion of the sinus from which it arises, the epithelium is of the same differentiated type, but here the pale-staining cells are much larger and more prominent than they are further cranially, their cytoplasm eosinophilic and their nuclei very small (Pl. 2, fig. 9). The remainder of the pars pelvina is still lined by the same undifferentiated type of epithelium as in the earlier stages.
  
The crown—rump length of this specimen is unfortunately not known, but it
 
shows a slightly later stage of development than the 112 mm. foetus. There is now
 
a marked dorso-ventral elongation of the pars phallica and a relative and absolute
 
shortening of the pars pelvina compared with the 94 mm. foetus. Though this
 
change of shape has slightly modified the relative positions of the folds in the sinus
 
wall their pattern remains essentially the same (Text-fig. 3).
 
  
Text-fig. 3. 16;» week foetus. Median sagittal section and the corresponding transverse sections
+
The lower part of the utero-vaginal canal is lined by a stratified polygonal epithelium, and the first sign of the differentiation of the surrounding mesoderm which marks the position of the future external os (Bulmer, 1955) indicates that this epithelium lines the entire ‘vaginal ’ portion of the canal, the uterine segment retaining its original columnar epithelium.
through the sinus and the lower end of the utero-vaginal canal (x 13;). The arrow at 3
 
indicates the level of the cranial tips of the sinus upgrowth, on either side of the lower end of
 
the utero-vaginal canal. Other lettering and shading as for Text-fig. 1.
 
  
The sinus upgrowth extends cranially for a distance of about 1-6 mm.—approxi-
+
==16.5 week Foetus==
mately half the extent of the future vagina as indicated by the site of the external os.
 
In most of its extent the upgrowth forms a solid transversely elongated epithelial
 
plate, and cranially it extends for a short distance as bilateral wings on either side
 
of the lower end of the utero-vaginal canal. Its epithelium is again diiferentiated
 
into -basal and superficial zones, and the thickness of section (12 ,u) seems to
 
accentuate the distinction between Miillerian and sinus epithelia (Pl. 2, fig. 11).
 
The ‘vaginal’ portion of the utero-vaginal canal is lined by a four- or five-layered
 
Stratified Miillerian epithelium, and the superficial cells are now becoming more
 
flattened.
 
  
At its caudal end the sinus upgrowth joins the enlargement of the sinus which
+
The crown—rump length of this specimen is unfortunately not known, but it shows a slightly later stage of development than the 112 mm. foetus. There is now a marked dorso-ventral elongation of the pars phallica and a relative and absolute shortening of the pars pelvina compared with the 94 mm. foetus. Though this change of shape has slightly modified the relative positions of the folds in the sinus wall their pattern remains essentially the same (Text-fig. 3).
lies cranial and dorsal to the urethro-vaginal folds, unsplit by any mesodermal
 
septum, and this lower end of the upgrowth now shows three swellings of its epithelial
 
plate, one centrally and one on either side. In these swellings, and in the dorsal
 
The development of the humans vagina 497
 
  
enlargement of the sinus, the epithelium is rather different from that in the cranial
 
part of the sinus upgrowth. The internal cells are larger and the nuclei smaller, so
 
that the distinction between basal and superficial zones is much more apparent
 
(Pl. 2, fig. 12). In addition, particularly in the swellings of the sinus upgrowth, the
 
cytoplasm of the internal cells is eosinophilic, and the cell walls deeply stained.
 
The remainder of the pars pelvina, below and ventral to the urethro-vaginal folds,
 
is still lined by an undifferentiated type of epithelium, consisting of four or five
 
layers of small, darkly staining cells.
 
  
140 mm. foetus
+
'''Text-fig. 3.''' 16.5 week foetus. Median sagittal section and the corresponding transverse sections through the sinus and the lower end of the utero-vaginal canal (x 13;). The arrow at 3 indicates the level of the cranial tips of the sinus upgrowth, on either side of the lower end of the utero-vaginal canal. Other lettering and shading as for Text-fig. 1.
  
In this specimen many further developments are apparent. The sinus upgrowth
 
extends to the lower end of the cervical canal as a solid, transversely elongated
 
epithelial plate in which the basal and internal zones of cells can be distinguished.
 
Here it meets a stratified squamous Miillerian epithelium (Pl. 2, fig. 13), which
 
consists of very much smaller cells and lines the lower portion of the cervical canal
 
immediately above the sinus upgrowth, intervening between this and the columnar
 
epithelium of the rest of the uterus above. The vaginal fornices have not yet
 
appeared.
 
  
As the sinus upgrowth is followed caudally, it develops, about the middle of its
+
The sinus upgrowth extends cranially for a distance of about 1-6 mm. — approximately half the extent of the future vagina as indicated by the site of the external os. In most of its extent the upgrowth forms a solid transversely elongated epithelial plate, and cranially it extends for a short distance as bilateral wings on either side of the lower end of the utero-vaginal canal. Its epithelium is again diiferentiated into basal and superficial zones, and the thickness of section (12 ,u) seems to accentuate the distinction between Miillerian and sinus epithelia (Pl. 2, fig. 11). The ‘vaginal’ portion of the utero-vaginal canal is lined by a four- or five-layered Stratified Miillerian epithelium, and the superficial cells are now becoming more flattened.
cranio-caudal extent, enlargements similar to those seen at the lower end of the
 
upgrowth in the 16% week foetus—a large swelling centrally, and smaller swellings
 
at each lateral extremity. Traced further caudally these swellings become larger,
 
until eventually they merge together to form a single mass occupying about the
 
lower one-third of the vagina, rather heart-shaped in cross-section and with a large
 
central lumen (Text-fig. 4). In the swellings the vaginal epithelium consists of
 
a narrow basal zone of darkly staining cells, with relatively large nuclei, and a mass
 
of large internal pale-staining cells with very small nuclei, eosinophilic cytoplasm
 
and very deeply stained cell walls (Pl. 3, fig. 14). In the canalized portion of the
 
vagina the epithelium is very similar, with a thick zone of internal cells of which the
 
superficial layers are flattened. The lumen is filled by a mass of desquamated
 
material, and the PAS technique demonstrates that all but the basal cells of the
 
epithelial lining are loaded with glycogen. e
 
  
The lower end of the vagina communicates with the sinus by paired hymeneal
 
orifices (Text-fig. 4b and P1. 3, fig. 15), separated from each other by a small median
 
mesodermal septum, and the great enlargement of the lower end of the vagina has
 
resulted in the extension of its area of contact with the sinus, particularly on the
 
lateral and caudal aspects of the orifices (Text-fig. 40). In this way the hymen is
 
formed, consisting of a plate of dense connective tissue, lined above by vaginal
 
epithelium and below by the undifferentiated type of sinus epithelium which still
 
occupies the upper part of the sinus (Pl. 3, fig. 17').
 
  
Associated with the increasing area of contact between the vagina and the sinus
+
At its caudal end the sinus upgrowth joins the enlargement of the sinus which lies cranial and dorsal to the urethro-vaginal folds, unsplit by any mesodermal septum, and this lower end of the upgrowth now shows three swellings of its epithelial plate, one centrally and one on either side. In these swellings, and in the dorsal enlargement of the sinus, the epithelium is rather different from that in the cranial part of the sinus upgrowth. The internal cells are larger and the nuclei smaller, so that the distinction between basal and superficial zones is much more apparent (Pl. 2, fig. 12). In addition, particularly in the swellings of the sinus upgrowth, the cytoplasm of the internal cells is eosinophilic, and the cell walls deeply stained. The remainder of the pars pelvina, below and ventral to the urethro-vaginal folds, is still lined by an undifferentiated type of epithelium, consisting of four or five layers of small, darkly staining cells.
which gives rise to the hymen, the configuration of the sinus itself shows a consider-
 
able change from the stage represented by the 16% week foetus. The pars pelvina, as
 
judged by the site of entry of the ducts of Bartholin’s glands (Text-fig. 4), is now
 
very short, and the original system of longitudinal folds, though it can still be
 
followed, has become modified by the change in shape of this part of the sinus.
 
498 D. Bulmer
 
  
A striking feature, which seems to be associated with the invagination of the upper
+
==140 mm Foetus==
part of the dorsal wall of the sinus by the lower end of the vagina, is the accentuation
 
of the upper end of the lateral fold, now lying parallel with the posterior portion
 
of the hymen and separated from it by an upward extension of the dorso-lateral
 
sinus bay—the bay which, at a lower level (Text-fig. 4), receives the ducts of
 
Bartho1in’s glands. The dorso-lateral bay extends cranially and ventrally on the
 
lower aspect of the hymen as far as the hymeneal orifices, where it terminates as
 
the lateral fold becomes continuous with the hymeneal fold. In addition, it gives off
 
a cranial diverticulum which ascends for a short distance on the lateral aspect of
 
  
+
In this specimen many further developments are apparent. The sinus upgrowth extends to the lower end of the cervical canal as a solid, transversely elongated epithelial plate in which the basal and internal zones of cells can be distinguished. Here it meets a stratified squamous Miillerian epithelium (Pl. 2, fig. 13), which consists of very much smaller cells and lines the lower portion of the cervical canal immediately above the sinus upgrowth, intervening between this and the columnar epithelium of the rest of the uterus above. The vaginal fornices have not yet appeared.
  
Ill V /
 
  
Text-fig. 4. 140 mm. foetus. Median sagittal section through the vagina and the sinus, with the
+
As the sinus upgrowth is followed caudally, it develops, about the middle of its cranio-caudal extent, enlargements similar to those seen at the lower end of the upgrowth in the 16% week foetus—a large swelling centrally, and smaller swellings at each lateral extremity. Traced further caudally these swellings become larger, until eventually they merge together to form a single mass occupying about the lower one-third of the vagina, rather heart-shaped in cross-section and with a large central lumen (Text-fig. 4). In the swellings the vaginal epithelium consists of a narrow basal zone of darkly staining cells, with relatively large nuclei, and a mass of large internal pale-staining cells with very small nuclei, eosinophilic cytoplasm and very deeply stained cell walls (Pl. 3, fig. 14). In the canalized portion of the vagina the epithelium is very similar, with a thick zone of internal cells of which the superficial layers are flattened. The lumen is filled by a mass of desquamated material, and the PAS technique demonstrates that all but the basal cells of the epithelial lining are loaded with glycogen.
corresponding transverse sections (x 6§). The stippling indicates the vaginal epithelium,
 
and the vestibule is shown only in outline. Because of the dilatation of the upper end of the
 
sinus it is not practicable to indicate the folds of its wall in the median sagittal section.
 
However, the dorsal margin of the lower part of the lateral fold is shown by the dotted line,
 
and the small inset figure shows the outline (dotted line) of the upper end of the dorso-lateral
 
sinus bay and its cranial diverticulum in relation to the margins of the vaginal and sinus
 
epithelia (continuous lines) and to the hymeneal orifices (interrupted line). hy—hy’ indicates
 
the level of the hymeneal orifices in relation to the median sagittal section. Other lettering
 
as for Text-fig. 1. It will be seen that the change in the position of the lateral fold in this
 
specimen, and to an even greater extent in the next (Text-fig. 5), differs from that described
 
by Mijsberg (1924). The dorso-lateral bay is rotated relatively upwards and backwards with
 
the downgrowth of the vagina into the sinus. According to Mijsberg, this bay is rotated
 
upwards and forwards, an opinion for which the present material offers no evidence.
 
  
the lower end of the Vagina (Pl. 3, figs. 15, 16), and presumably represents the
 
cranial extremity of the dorso-lateral bay of the 16% week stage, maintaining its
 
position despite the relative downgrowth of the lower end of the vagina.
 
  
The hymeneal folds, bounding the outer margins of the paired hymeneal orifices,
+
The lower end of the vagina communicates with the sinus by paired hymeneal orifices (Text-fig. 4b and P1. 3, fig. 15), separated from each other by a small median mesodermal septum, and the great enlargement of the lower end of the vagina has resulted in the extension of its area of contact with the sinus, particularly on the lateral and caudal aspects of the orifices (Text-fig. 40). In this way the hymen is formed, consisting of a plate of dense connective tissue, lined above by vaginal epithelium and below by the undifferentiated type of sinus epithelium which still occupies the upper part of the sinus (Pl. 3, fig. 17').
represent the dorsal margins of the urethro-vaginal folds of the earlier stages. In
 
the same way they form the boundary between the differentiated and undifferenti-
 
ated types of sinus epithelium, and it is by the enlargement of the area of dif-
 
ferentiated epithelium——now the lower end of the vagina——and its downgrowth
 
relative to the urogenital sinus that the hymen is formed. The mesodermal septum
 
between the two hymeneal orifices seems to differ in origin from the remainder of
 
The development of the human vagina 499
 
  
the hymen, and probably results from the further development of a septum such as
 
occurs in the 112 mm. foetus, splitting the root of the sinus upgrowth. By the
 
enlargement and downgrowth of the lower end of the vagina the septum is pro-
 
jected forwards to divide the space between the dorsal margins of the urethro-
 
vaginal folds—in other words, to split the hymeneal orifice. The mesodermal septum
 
of the 140 mm. stage is therefore lined on both its ventral and dorsal aspects by
 
vaginal epithelium.
 
  
180 mm. foetus
+
Associated with the increasing area of contact between the vagina and the sinus which gives rise to the hymen, the configuration of the sinus itself shows a considerable change from the stage represented by the 16% week foetus. The pars pelvina, as judged by the site of entry of the ducts of Bartholin’s glands (Text-fig. 4), is now very short, and the original system of longitudinal folds, though it can still be followed, has become modified by the change in shape of this part of the sinus.  
  
The enlargement and canalisation of the vagina now extends throughout its
 
entire length, and the fornices are well established. An important change is the
 
disappearance of the zone of stratified squamous Miillerian epithelium from the
 
lower portion of the cervical canal, and the sinus epithelium of the vagina meets the
 
columnar epithelium of the uterus just inside the external os. Here there is a very
 
clear line of distinction between the two epithelia (Pl. 3, fig. 18). Both give a strongly
 
positive PAS reaction, granular in the vaginal epithelium and diffuse in the columnar
 
cells of the cervix, but in the latter this reaction is not affected by previous salivary
 
digestion.
 
  
The vagina is lined by a very thick stratified squamous epithelium (Pl. 3, fig. 19),
+
A striking feature, which seems to be associated with the invagination of the upper part of the dorsal wall of the sinus by the lower end of the vagina, is the accentuation of the upper end of the lateral fold, now lying parallel with the posterior portion of the hymen and separated from it by an upward extension of the dorso-lateral sinus bay—the bay which, at a lower level (Text-fig. 4), receives the ducts of Bartho1in’s glands. The dorso-lateral bay extends cranially and ventrally on the lower aspect of the hymen as far as the hymeneal orifices, where it terminates as the lateral fold becomes continuous with the hymeneal fold. In addition, it gives off a cranial diverticulum which ascends for a short distance on the lateral aspect of the lower end of the Vagina (Pl. 3, figs. 15, 16), and presumably represents the cranial extremity of the dorso-lateral bay of the 16.5 week stage, maintaining its position despite the relative downgrowth of the lower end of the vagina.
in which it is possible to distinguish four cellular zones. The basal zone is formed by
 
three or four layers of small cubical cells, with relatively large nuclei and basophil
 
cytoplasm. The next zone consists of seven or eight layers of much larger cells,
 
with relatively much smaller nuclei and pale, acidophil cytoplasm. The deeper
 
layers of this zone consist of polygonal cells, with deeply stained cell walls, but the
 
three or four superficial layers are formed by very flattened cells, with much
 
thicker cell walls. The third zone consists of about ten layers of large, clear-staining
 
polygonal cells, less flattened and with thinner cell walls than the most superficial
 
cells of the second zone. The nuclei are very small, and are absent from many of the
 
cells. The innermost zone is formed by four or five layers of cells, similar to those of
 
the third zone but more flattened. Many of the cells are without nuclei, and the
 
nuclei which are present are very small and pyknotic.
 
  
Glycogen is extremely abundant in the vaginal epithelium in all but the basal zone
 
of cells, as shown by staining with Best’s ammoniacal carmine and by the PAS
 
technique. It is generally located as large granules, sometimes almost filling the
 
cytoplasm of the cell, and is usually, but not always, restricted to the part of the
 
cell on the proximal side of the nucleus. In addition, the cell walls of the three
 
superficial zones show a positive PAS reaction after previous salivary digestion,
 
similar to that demonstrated by Wislocki, Fawcett & Dempsey (1951) in the
 
vaginal epithelium of the adult.
 
  
A further development from the 140 mm. stage is the lining of the under surface
 
of the hymen and the adjacent portion of the vestibule by an epithelium similar to
 
the vaginal epithelium, though rather thinner. Associated with the further relative
 
downgrowth of the lower end of the vagina, and the resulting more horizontal
 
position of the hymen (Text-fig. 5), the pars pelvina has almost disappeared. In
 
fact, the shape of the sinus is so distorted from its original form that the distinction
 
between pars pelvina and pars phallica now has little meaning.-
 
  
31 Anat. 91
 
500 D. Bulmer
 
  
By this stage the sinus extends further dorsally in relation to the under surface
+
'''Text-fig. 4.''' 140 mm. foetus. Median sagittal section through the vagina and the sinus, with the corresponding transverse sections (x 6§). The stippling indicates the vaginal epithelium, and the vestibule is shown only in outline. Because of the dilatation of the upper end of the sinus it is not practicable to indicate the folds of its wall in the median sagittal section. However, the dorsal margin of the lower part of the lateral fold is shown by the dotted line, and the small inset figure shows the outline (dotted line) of the upper end of the dorso-lateral sinus bay and its cranial diverticulum in relation to the margins of the vaginal and sinus epithelia (continuous lines) and to the hymeneal orifices (interrupted line). hy—hy’ indicates the level of the hymeneal orifices in relation to the median sagittal section. Other lettering as for Text-fig. 1. It will be seen that the change in the position of the lateral fold in this specimen, and to an even greater extent in the next (Text-fig. 5), differs from that described by Mijsberg (1924). The dorso-lateral bay is rotated relatively upwards and backwards with the downgrowth of the vagina into the sinus. According to Mijsberg, this bay is rotated upwards and forwards, an opinion for which the present material offers no evidence.
of the hymen, and the dorso-lateral sinus bays are very prominent, forming a
 
dilatation of the vestibule immediately beneath the hymen (Text-figs. 5a, b). They
 
extend further ventrally than in the 140 mm. foetus, reaching forwards around the
 
sides of the anterior portion of the hymen. As before, they send short diverticula
 
cranially, on either side of the lower end of the vagina. The hymenal orifice is
 
unsplit.
 
  
200 mm. foetus
 
  
This specimen shows little further change, but the sagittal plane of section gives
+
The hymeneal folds, bounding the outer margins of the paired hymeneal orifices, represent the dorsal margins of the urethro-vaginal folds of the earlier stages. In the same way they form the boundary between the differentiated and undifferentiated types of sinus epithelium, and it is by the enlargement of the area of differentiated epithelium - now the lower end of the vagina — and its downgrowth relative to the urogenital sinus that the hymen is formed. The mesodermal septum between the two hymeneal orifices seems to differ in origin from the remainder of the hymen, and probably results from the further development of a septum such as occurs in the 112 mm. foetus, splitting the root of the sinus upgrowth. By the enlargement and downgrowth of the lower end of the vagina the septum is projected forwards to divide the space between the dorsal margins of the urethro-vaginal folds — in other words, to split the hymeneal orifice. The mesodermal septum of the 140 mm. stage is therefore lined on both its ventral and dorsal aspects by vaginal epithelium.
a very clear picture of the penetration of the lower end of the cervical canal by the
 
vaginal epithelium, to a distance of about 3 mm. above the external os.
 
  
375 mm. foetus
+
==180 mm Foetus==
  
The vaginal epithelium is now considerably thinner, but the lumen is filled with
+
The enlargement and canalisation of the vagina now extends throughout its entire length, and the fornices are well established. An important change is the disappearance of the zone of stratified squamous Miillerian epithelium from the lower portion of the cervical canal, and the sinus epithelium of the vagina meets the columnar epithelium of the uterus just inside the external os. Here there is a very clear line of distinction between the two epithelia (Pl. 3, fig. 18). Both give a strongly positive PAS reaction, granular in the vaginal epithelium and diffuse in the columnar cells of the cervix, but in the latter this reaction is not affected by previous salivary digestion.
cell debris, suggesting that the decrease in thickness may be largely due to de-
 
squamation of the superficial cell layers. Only three cellular zones can be dis-
 
tinguished (Pl. 3, fig. 20). In the basal zone there are usually three layers of small
 
cubical cells, with large nuclei and basophil cytoplasm. The intermediate zone is
 
  
U
 
  
<?/
+
The vagina is lined by a very thick stratified squamous epithelium (Pl. 3, fig. 19), in which it is possible to distinguish four cellular zones. The basal zone is formed by three or four layers of small cubical cells, with relatively large nuclei and basophil cytoplasm. The next zone consists of seven or eight layers of much larger cells, with relatively much smaller nuclei and pale, acidophil cytoplasm. The deeper layers of this zone consist of polygonal cells, with deeply stained cell walls, but the three or four superficial layers are formed by very flattened cells, with much thicker cell walls. The third zone consists of about ten layers of large, clear-staining polygonal cells, less flattened and with thinner cell walls than the most superficial cells of the second zone. The nuclei are very small, and are absent from many of the cells. The innermost zone is formed by four or five layers of cells, similar to those of the third zone but more flattened. Many of the cells are without nuclei, and the nuclei which are present are very small and pyknotic.
0 v
 
00 * o
 
.
 
  
3 C
 
  
Text-fig. 5. 180 mm. foetus. Median sagittal section through the lower end of the vagina and the
+
Glycogen is extremely abundant in the vaginal epithelium in all but the basal zone of cells, as shown by staining with Best’s ammoniacal carmine and by the PAS technique. It is generally located as large granules, sometimes almost filling the cytoplasm of the cell, and is usually, but not always, restricted to the part of the cell on the proximal side of the nucleus. In addition, the cell walls of the three superficial zones show a positive PAS reaction after previous salivary digestion, similar to that demonstrated by Wislocki, Fawcett & Dempsey (1951) in the vaginal epithelium of the adult.
vestibule, with the corresponding coronal sections ( x 4). The dotted line in the sagittal section
 
shows the relative extent of the dorso-lateral bays. The coronal sections are shown with their
 
cranial ends towards the top. a, urethra; v, vagina; h, hymeneal orifice; db, dorso-lateral
 
sinus bay; cd, cranial diverticulum of dorso-lateral sinus bay.
 
  
 
  
u
+
A further development from the 140 mm. stage is the lining of the under surface of the hymen and the adjacent portion of the vestibule by an epithelium similar to the vaginal epithelium, though rather thinner. Associated with the further relative downgrowth of the lower end of the vagina, and the resulting more horizontal position of the hymen (Text-fig. 5), the pars pelvina has almost disappeared. In fact, the shape of the sinus is so distorted from its original form that the distinction between pars pelvina and pars phallica now has little meaning.
£/ cd.
 
nh
 
db
 
b
 
  
formed by four or five layers of much larger polygonal cells, with relatively smaller
 
nuclei and deeply staining cell walls. Superficially there are two or three layers of
 
large flattened cells with small pyknotic nuclei. The superficial and intermediate
 
zones are not clearly distinct from each other, and both are rich in glycogen granules.
 
It is possible that these two zones represent the second zone of the epithelium of the
 
180 mm. foetus, the third and fourth zones having been desquamated. Again the
 
cell walls give a positive PAS reaction after salivary digestion.
 
  
The sinus shows the further progress of the developmental changes noticed at the
+
By this stage the sinus extends further dorsally in relation to the under surface of the hymen, and the dorso-lateral sinus bays are very prominent, forming a dilatation of the vestibule immediately beneath the hymen (Text-figs. 5a, b). They extend further ventrally than in the 140 mm. foetus, reaching forwards around the sides of the anterior portion of the hymen. As before, they send short diverticula cranially, on either side of the lower end of the vagina. The hymenal orifice is unsplit.
180 mm. stage. The dorso-lateral bays extend still further forwards, now reaching
 
around the urethral orifice, and the dorsal extension of the sinus in relation to the
 
under surface of the hymen is still more marked. The whole of the upper part of the
 
The development of the human vagina 501
 
  
sinus is lined by an epithelium similar to that of the vagina, and now of about the
+
==200 mm Foetus==
same thickness.
 
  
1 month infant
+
This specimen shows little further change, but the sagittal plane of section gives a very clear picture of the penetration of the lower end of the cervical canal by the vaginal epithelium, to a distance of about 3 mm. above the external os.
  
Little change is noticed in this specimen, except in the character of the vaginal
+
==375 mm Foetus==
epithelium (Pl. 3, fig. 21). This is considerably thinner than in the later foetal stages
 
and consists mainly of polygonal cells with relatively large nuclei, deeply staining
 
cytoplasm and indistinct cell walls. Glycogen is no longer present, and the cell walls
 
no longer give a positive PAS reaction.
 
  
DISCUSSION
+
The vaginal epithelium is now considerably thinner, but the lumen is filled with cell debris, suggesting that the decrease in thickness may be largely due to desquamation of the superficial cell layers. Only three cellular zones can be distinguished (Pl. 3, fig. 20). In the basal zone there are usually three layers of small cubical cells, with large nuclei and basophil cytoplasm. The intermediate zone is formed by four or five layers of much larger polygonal cells, with relatively smaller nuclei and deeply staining cell walls. Superficially there are two or three layers of large flattened cells with small pyknotic nuclei. The superficial and intermediate zones are not clearly distinct from each other, and both are rich in glycogen granules. It is possible that these two zones represent the second zone of the epithelium of the 180 mm. foetus, the third and fourth zones having been desquamated. Again the cell walls give a positive PAS reaction after salivary digestion.
  
There can be little doubt that the epithelium of the human vagina is entirely
 
derived from an upgrowth of sinus cells, as Vilas (1932), Kempermann (1935) and
 
Meyer (1934-38) claimed, but the manner of formation of this upgrowth does not
 
seem to be completely in accord with their findings. Vilas believed that the epi-
 
thelium in the dorsal wall of the sinus proliferated in two different ways. An inner
 
proliferation of pale-staining cells grew ventrally and medially in the internal layers
 
of the dorsal sinus wall, meeting its fellow to form a crest which projected ventrally
 
into the sinus lumen. An outer proliferation of darkly staining cells grew dorsally,
 
displaced the Miillerian cells from the Miillerian tubercle and extended cranially as
 
an epithelial plate, subsequently canalized to form the vagina. The views of Meyer
 
and Kempermann were essentially similar.
 
  
It is interesting to compare this with Kofi"s account (1933) of the origin of the
 
‘sino-vaginal bulbs’, evaginations of the dorso-lateral aspect of the sinus on each
 
side. Koff found that their epithelium was different from that of the rest of the
 
sinus, consisting of well-marked basal and superficial zones, the basal cells darkly
 
staining and the superficial cells pale-staining. The bulbs became larger and
 
eventually fused with each other to form a solid cellular mass, which displaced the
 
Miillerian tissue dorsally and cranially and eventually became canalized as the
 
lower one-fifth of the vagina. The sino-vaginal bulbs seem to be the structures
 
which have here been termed the dorso-lateral projections. In the same way they
 
were joined by the lower ends of the Wolffian ducts, when these persisted, and
 
carried the attachments of the duets with them as they extended cranially. Koff
 
did not mention any proliferation of darkly staining cells from the intermediate
 
portion of the dorsal wall of the sinus, such as occurs in the 65 mm., 68 mm. and
 
14-week foetuses of this present collection, and would presumably regard this
 
proliferation as an early stage in the fusion of the sino-vaginal bulbs.
 
  
Up to a point, the findings of this present investigation combine both these views
 
on the initial origin of the sinus contribution to the vagina, the sinus upgrowth
 
taking origin from all three of the elements associated with the activity of the
 
  
. dorsal wall of the sinus, first noticed in the 65 mm. foetus. The junction of the
+
'''Text-fig. 5.''' 180 mm. foetus. Median sagittal section through the lower end of the vagina and the vestibule, with the corresponding coronal sections ( x 4). The dotted line in the sagittal section shows the relative extent of the dorso-lateral bays. The coronal sections are shown with their cranial ends towards the top. a, urethra; v, vagina; h, hymeneal orifice; db, dorso-lateral sinus bay; cd, cranial diverticulum of dorso-lateral sinus bay.
  
persistent lower end of the left Wolffian duct with the sinus upgrowth in the
 
94 mm. specimen indicates that, at any rate in this foetus, the dorso-lateral pro-
 
jection must have participated in the formation of the upgrowth. On the other
 
hand, in the 65 mm. foetus there seems no doubt as to the entity of the inter-
 
mediate proliferation of darkly staining cells, and their contribution to the sinus
 
31-2
 
502 D. Bulmer
 
  
upgrowth cannot be ignored. Only by the fusion of the three initial elements, by
 
the 94 mm. stage, is the single sinus upgrowth produced. It is interesting that the
 
formation of the sinus upgrowth in the human foetus bears such a close similarity
 
to the initial origin of the lower vaginal segment in the sheep (Bulmer, 1956). There
 
may be no great significance in the distinction between the dorso-lateral projections
 
and the intermediate proliferation of darkly staining cells, all three representing a
 
continuous cellular proliferation from this area of the sinus wall. There seems little
 
doubt, however, of the identification of the dorso-lateral projections with Kofi"s
 
sino-vaginal bulbs, and of the intermediate proliferation with the outer sinus
 
proliferation of Vilas.
 
  
In many instances, it appears, the root of the sinus upgrowth is split at its origin
+
The sinus shows the further progress of the developmental changes noticed at the 180 mm. stage. The dorso-lateral bays extend still further forwards, now reaching around the urethral orifice, and the dorsal extension of the sinus in relation to the under surface of the hymen is still more marked. The whole of the upper part of the sinus is lined by an epithelium similar to that of the vagina, and now of about the same thickness.
from the dorsal wall of the sinus by the inclusion of a small mesodermal septum.
 
Vilas pointed out that in his early foetuses, from the 38 mm. stage onwards, a small
 
mass of mesoderm interrupted the contact between the Miillerian epithelium and the
 
dorsal wall of the sinus in the midline, and this has been noticed here in the 28, 42
 
and 50 mm. foetuses. Vilas described the initial bilateral origin of the darkly staining
 
sinus proliferation, the two origins then fusing to form a single sinus upgrowth. In
 
the 65 mm. foetus, described here, there is no sign of such a bilateral origin, but in
 
the 68 mm. foetus the proliferation is split by a small mesodermal septum. The
 
inclusion of a mesodermal septum in the root of the sinus upgrowth is most prob-
 
ably a result of the persistence of such a septum at the Mfillerian tubercle, and this
 
would suggest that the darkly staining proliferation only arises where the sinus is
 
actually in contact with Miillerian cells. The persistence of such a septum, as in the
 
112 mm. foetus, and its development into a hymeneal septum, as in the 140 mm.
 
foetus, must be fairly common, and occurred in many of the specimens examined by
 
Meyer (1934-38). The persistence of a more extensive septum in the utero-vaginal
 
canal would account, in a similar manner, for a congenital duplication of the vagina.
 
  
The further development of the sinus upgrowth, after the 94 mm. stage, is of some
+
==1 month Infant==
interest. Vilas found that as the Miillerian epithelium receded before the advancing
 
plate of sinus epithelium the lower end of the utero-vaginal canal, including its
 
whole ‘vaginal’ portion, became completely occluded by the proliferation of its
 
lining cells. A solid vaginal plate was thereby formed, composed of Miillerian tissue
 
above and sinus tissue below, but the sinus epithelium gradually extended further
 
and further cranially until eventually the Miillerian epithelium was completely
 
displaced from the vaginal plate. In the series of foetuses examined here the
 
occlusion of the lower end of the utero-vaginal canal is not a prominent feature. It
 
is first seen at the 65 mm. stage and persists until the Miillerian epithelium is
 
completely excluded from the vagina, but it never involves more than a short
 
segment. It is to be noted, however, that the Stratification of the epithelium of the
 
utero-vaginal canal does extend, apparently by the 94 mm. stage, throughout the
 
entire ‘vaginal’ portion of the canal.
 
  
Koff also described a ‘ primitive vaginal plate ’, formed in its lower portion by the
+
Little change is noticed in this specimen, except in the character of the vaginal epithelium (Pl. 3, fig. 21). This is considerably thinner than in the later foetal stages and consists mainly of polygonal cells with relatively large nuclei, deeply staining cytoplasm and indistinct cell walls. Glycogen is no longer present, and the cell walls no longer give a positive PAS reaction.
solid epithelial mass of the sino-vaginal bulbs, and in its upper portion from the
 
occlusion of the ‘vaginal’ portion of the utero-vaginal canal by the proliferation of
 
its lining cells. In this solid vaginal plate Koff claimed that he was able to dis-
 
tinguish histologically between the sinus and Miillerian components, and only after
 
The development of the human vagina 503
 
  
the 142 mm. stage was this distinction no longer apparent. He assumed that the
+
==Discussion==
relative proportions of the two epithelia remained unchanged after this stage, the
 
sinus epithelium being restricted to the lower one-fifth of the vagina.
 
  
Unfortunately, Koff showed no microphotograph of the epithelial distinction
+
There can be little doubt that the epithelium of the human vagina is entirely derived from an upgrowth of sinus cells, as Vilas (1932), Kempermann (1935) and Meyer (1934-38) claimed, but the manner of formation of this upgrowth does not seem to be completely in accord with their findings. Vilas believed that the epithelium in the dorsal wall of the sinus proliferated in two different ways. An inner proliferation of pale-staining cells grew ventrally and medially in the internal layers of the dorsal sinus wall, meeting its fellow to form a crest which projected ventrally into the sinus lumen. An outer proliferation of darkly staining cells grew dorsally, displaced the Miillerian cells from the Miillerian tubercle and extended cranially as an epithelial plate, subsequently canalized to form the vagina. The views of Meyer and Kempermann were essentially similar.
between the components of his primitive vaginal plate, but the criterion which he
 
used for the identification of the sinus epithelium was its differentiation into
 
external darkly staining and internal pale-staining zones. It has been noticed in
 
the series of foetuses described here that after the 94 mm. stage the internal cells in
 
the cranial part of the sinus upgrowth are much less pale-staining than they are
 
further caudally. For instance, in the 16% week foetus the large, markedly pale-
 
staining cells are restricted to the enlarged portion of the dorsal wall of the sinus
 
and to the swellings at the caudal end of the sinus upgrowth. Indeed, Koff seems
 
to have identified the two laterally placed swellings with the sino-vaginal bulbs
 
themselves—a conclusion which is difficult to follow and for which there is no
 
evidence in the material described here. The epithelium at the cranial end of the
 
sinus upgrowth is of the same essential character as that further caudally. There is
 
no evidence of any sharp histological distinction in the vaginal mass except the one
 
which has been identified as the junction of the cranial end of the sinus upgrowth
 
with the caudal end of the Miillerian tissue. Koff’s description offers no expla-
 
nation for the very marked distinction between the two, occurring about half-way
 
up the ‘vagina’ in the 16% week foetus.
 
  
The most likely explanation for the histological differences between the cranial
 
and caudal ends of the sinus upgrowth is that the differentiation of its cells progresses
 
from below upwards. Thus, the cells of the caudal end of the upgrowth in the 112 mm.
 
and 16:} week foetuses, when the internal cells are larger, their nuclei smaller and the
 
cell walls deeply stained with eosin, are similar to those occupying the whole of the
 
lower half of the vagina in the 140 mm. foetus. The transversely elongated plate of
 
the vagina appears to differentiate, at each particular stage, by first enlarging to
 
form swellings. The epithelium correspondingly proliferates and the internal cells
 
become large, with small nuclei and deeply stained cell walls. The swellings become
 
still larger, and confluent with each other, the central cells then desquamating to
 
form the vaginal lumen. The 140 mm. foetus shows later and later stages of this
 
process as the sinus upgrowth is followed further and further caudally. The vaginal
 
epithelium continues to proliferate, presumably under the influence of hormonal
 
stimulation, and it is interesting to compare its structure in the two older foetuses
 
with the adult vaginal epithelium as described by Papanicolou, Traut & Marchetti
 
(1948), and more particularly, in view of the probable hormonal influences at work,
 
with the vaginal epithelium of the pregnant woman, described by Smith & Brunner
 
(1934)
 
  
As indicated above, many earlier workers have denied the participation of sinus
+
It is interesting to compare this with Koff's account (1933) of the origin of the ‘sino-vaginal bulbs’, evaginations of the dorso-lateral aspect of the sinus on each side. Koff found that their epithelium was different from that of the rest of the sinus, consisting of well-marked basal and superficial zones, the basal cells darkly staining and the superficial cells pale-staining. The bulbs became larger and eventually fused with each other to form a solid cellular mass, which displaced the Miillerian tissue dorsally and cranially and eventually became canalized as the lower one-fifth of the vagina. The sino-vaginal bulbs seem to be the structures which have here been termed the dorso-lateral projections. In the same way they were joined by the lower ends of the Wolffian ducts, when these persisted, and carried the attachments of the duets with them as they extended cranially. Koff did not mention any proliferation of darkly staining cells from the intermediate portion of the dorsal wall of the sinus, such as occurs in the 65 mm., 68 mm. and 14-week foetuses of this present collection, and would presumably regard this proliferation as an early stage in the fusion of the sino-vaginal bulbs.
epithelium in the formation of the vagina. Berry Hart (1896, 1901 and 1911) and
 
Mijsberg (1924) described a contribution to the vagina from the ‘Wolflian bulbs’,
 
proliferations of the epithelium of the lower ends of the Wolffian ducts. There
 
seems no doubt that the Wolifian bulbs were the dorso-lateral projections, and
 
there is no evidence that these latter arise from Wolflian epithelium. Their cells are
 
unlike the cubical Wolffian cells which lie dorsal to them, and much more closely
 
504 D. Bulmer
 
  
resemble those of the dorsal sinus wall. Berry Hart believed that the epithelium
 
of the Wolffian bulbs extended throughout the entire vagina, while Mijsberg, in
 
a sense less correctly, restricted the Wolffian contribution to a lower vaginal
 
segment. His reasons for this were similar to those which influenced Koff to believe
 
that the sino-vaginal bulbs formed only the lower end of the vagina.
 
  
Other authors have held to the view that the human vagina is entirely derived
+
Up to a point, the findings of this present investigation combine both these views on the initial origin of the sinus contribution to the vagina, the sinus upgrowth taking origin from all three of the elements associated with the activity of the dorsal wall of the sinus, first noticed in the 65 mm. foetus. The junction of the persistent lower end of the left Wolffian duct with the sinus upgrowth in the 94 mm. specimen indicates that, at any rate in this foetus, the dorso-lateral projection must have participated in the formation of the upgrowth. On the other hand, in the 65 mm. foetus there seems no doubt as to the entity of the intermediate proliferation of darkly staining cells, and their contribution to the sinus upgrowth cannot be ignored. Only by the fusion of the three initial elements, by the 94 mm. stage, is the single sinus upgrowth produced. It is interesting that the formation of the sinus upgrowth in the human foetus bears such a close similarity to the initial origin of the lower vaginal segment in the sheep (Bulmer, 1956). There may be no great significance in the distinction between the dorso-lateral projections and the intermediate proliferation of darkly staining cells, all three representing a continuous cellular proliferation from this area of the sinus wall. There seems little doubt, however, of the identification of the dorso-lateral projections with Kofi"s sino-vaginal bulbs, and of the intermediate proliferation with the outer sinus proliferation of Vilas.
from the Miillerian utero-vaginal canal. Bloomfield & Frazer (1927) illustrated a
 
section rather similar to the ones shown in P1. 1, figs. 4, 5 and 6, for the 65 mm.
 
foetus, but their interpretation was very different, as they believed that the pale-
 
staining cells in the dorsal sinus wall were the Miillerian cells breaking through into
 
the sinus at the Miillerian tubercle. It is clear that the findings in the 65 mm. foetus
 
make such a view untenable, and this misinterpretation presumably led Bloomfield &
 
Frazer to think that the whole extent of the differentiated type of sinus epithelium
 
was of Miillerian origin.
 
  
While the sinus origin of the vaginal epithelium appears to be established, one
 
or two points of detail merit further consideration. From the earliest stage
 
examined, represented by the 28 mm. foetus, the epithelium which lines the part
 
of the sinus from which the sinus upgrowth later arises differs from that of the rest
 
of the pars pelvina in consisting of two cellular zones——darkly staining cells deeply
 
and pale-staining cells superficially. So far, it has been tacitly assumed that both
 
these cell types are of sinus origin, but other workers have placed different inter-
 
pretations upon them. Vilas (1932) believed that the darkly staining cells were of
 
sinus origin, but was prepared to accept that the pale-staining cells were Wolffian,
 
growing ventrally and medially in the dorsal wall of the sinus to form the ventrally
 
projecting Wolflsche Kamm, identified by Kempermann (1931) and evident in the
 
65 mm. foetus of this present investigation. Kempermann (1935) also believed that
 
the pale-staining cells were Wolffian in origin, but that they later completely
 
disappeared. The pale-staining cells in the internal layers of the sinus upgrowth at
 
a stage such as that represented by the 94 mm. foetus of this collection were not the
 
Wolffian cells, but a new generation of cells derived from the sinus. Meyer (1934-38),
 
however, believed that the pale-staining Wolffian cells did persist into later foetal
 
life, identifying them with the large pale-staining cells such as occur at the root of
 
the sinus upgrowth in the 112 mm. and 16% week foetuses.
 
  
This question does not seem possible of solution by ordinary histological methods.
+
In many instances, it appears, the root of the sinus upgrowth is split at its origin from the dorsal wall of the sinus by the inclusion of a small mesodermal septum. Vilas pointed out that in his early foetuses, from the 38 mm. stage onwards, a small mass of mesoderm interrupted the contact between the Miillerian epithelium and the dorsal wall of the sinus in the midline, and this has been noticed here in the 28, 42 and 50 mm. foetuses. Vilas described the initial bilateral origin of the darkly staining sinus proliferation, the two origins then fusing to form a single sinus upgrowth. In the 65 mm. foetus, described here, there is no sign of such a bilateral origin, but in the 68 mm. foetus the proliferation is split by a small mesodermal septum. The inclusion of a mesodermal septum in the root of the sinus upgrowth is most probably a result of the persistence of such a septum at the Mfillerian tubercle, and this would suggest that the darkly staining proliferation only arises where the sinus is actually in contact with Miillerian cells. The persistence of such a septum, as in the 112 mm. foetus, and its development into a hymeneal septum, as in the 140 mm. foetus, must be fairly common, and occurred in many of the specimens examined by Meyer (1934-38). The persistence of a more extensive septum in the utero-vaginal canal would account, in a similar manner, for a congenital duplication of the vagina.
Nevertheless, the pale-staining cells in the dorsal wall of the sinus from the 28 mm.
 
stage onwards bear no obvious similarity to the cubical cells which line the Wolffian
 
ducts, and are distinct from the Wolffian cells which lie dorsal to them. It appears
 
just as reasonable to suppose that the pale-staining cells are derivatives of the
 
darkly staining basal cells, and that there is no incorporation of Wolffian cells in
 
the dorsal wall of the sinus at this stage. No such ingrowth occurs in other mammals,
 
and it seems unnecessary to postulate it in the human foetus. Nevertheless, it must
 
be admitted that the differentiation of the sinus epithelium from which the sinus
 
upgrowth arises is a remarkable feature, and it too has not been described in other
 
mammals.
 
  
Also of some significance is the problem of the behaviour of the lower ends of the
 
Wolifian ducts during the development of the vagina. Descriptions of the lower ends
 
The development of the human vagina 505
 
  
of the Wolffian ducts in female foetuses fall generally into two main categories. In
+
The further development of the sinus upgrowth, after the 94 mm. stage, is of some interest. Vilas found that as the Miillerian epithelium receded before the advancing plate of sinus epithelium the lower end of the utero-vaginal canal, including its whole ‘vaginal’ portion, became completely occluded by the proliferation of its lining cells. A solid vaginal plate was thereby formed, composed of Miillerian tissue above and sinus tissue below, but the sinus epithelium gradually extended further and further cranially until eventually the Miillerian epithelium was completely displaced from the vaginal plate. In the series of foetuses examined here the occlusion of the lower end of the utero-vaginal canal is not a prominent feature. It is first seen at the 65 mm. stage and persists until the Miillerian epithelium is completely excluded from the vagina, but it never involves more than a short segment. It is to be noted, however, that the Stratification of the epithelium of the utero-vaginal canal does extend, apparently by the 94 mm. stage, throughout the entire ‘vaginal’ portion of the canal.
the first are those which maintain that the Wolffian ducts continue to open into the
 
sinus at their original site, immediately lateral to the position of the Miillerian
 
tubercle. Thus, Meyer (1909) described the persistence of the lower ends of the
 
Wolflian ducts in a large number of older foetuses and new-born children, running
 
into the substance of the hymen and opening into the vestibule close beside the
 
hymeneal orifice. On the other hand, many other workers (Tourneux & Legay, 1884;
 
van Ackeren, 1889; Mijsberg, 1924; Koff, 1933) have described the cranial migration
 
of the lower ends of the Wolffian ducts to join the lower end of the vagina itself,
 
though the ducts degenerated very soon after and did not persist into late foetal life.
 
  
At first sight, the present investigation supports this latter view. In the 94 mm.
 
foetus the lower end of the left Wolffian duct joins the sinus upgrowth, indicating
 
that the dorso-lateral projection has carried the Wolffian remnant with it as it grew
 
cranially, while in none of the older foetuses was there any trace of the lower ends
 
of the Wolffian ducts. Nevertheless, this evidence is insufficient to suggest that the
 
lower ends of the Wolffian ducts never maintain their openings into the sinus beside
 
the original site of the Miillerian tubercle, particularly in view of the large number of
 
such cases described by Meyer (1909). At that time Meyer regarded these Wolffian
 
remnants as indicative of the entirely Miillerian origin of the vagina, but in his later
 
publications (1934-38) pointed out that they were equally in accord with the account
 
of vaginal development given by Vilas. The Wolffian ducts were not involved in the
 
proliferation which Vilas believed to form the epithelial plate of the vagina, and
 
were therefore left behind near the hymen. Nevertheless, the structures which
 
Meyer now identified as persistent Wolffian remnants do not appear to occupy the
 
same site as those which he had described earlier, but join the lower end of the
 
vagina on the upper aspect of the hymen. In other words, they have been carried
 
cranially for a short distance during the formation of the sinus upgrowth.
 
  
It may be that in some instances the lower ends of the Wolffian ducts are not
+
Koff also described a ‘ primitive vaginal plate ’, formed in its lower portion by the solid epithelial mass of the sino-vaginal bulbs, and in its upper portion from the occlusion of the ‘vaginal’ portion of the utero-vaginal canal by the proliferation of its lining cells. In this solid vaginal plate Koff claimed that he was able to distinguish histologically between the sinus and Miillerian components, and only after the 142 mm. stage was this distinction no longer apparent. He assumed that the relative proportions of the two epithelia remained unchanged after this stage, the sinus epithelium being restricted to the lower one-fifth of the vagina.
carried cranially with the sinus upgrowth to such a great extent as they have been
 
in the 94 mm. foetus, or indeed that they are not carried cranially at all. This may
 
be because the dorso-lateral projections do not play such a large part in the forma-
 
tion of the sinus upgrowth in these cases, or because the manner of their growth is
 
such as not to involve the lower ends of the Wolffian ducts. In other words, it is
 
possible, as von Lippmann suggested (1939), though with rather a different purpose,
 
that there is some variability in the behaviour of the lower ends of the Wolffian
 
ducts during the early stages of vaginal development. This is supported by the fact
 
that an ectopic ureter, presumably opening by a persistent Wolffian remnant, may
 
join either the vagina or the vestibule (Kermauner, 1909). It is also possible that
 
many of the structures which have been identified as persistent Wolffian remnants
 
were, in fact, not so. In the 140 mm. foetus the dorso-lateral sinus bays end above
 
by sending short diverticula upwards on either side of the lower end of the vagina,
 
lined by the undifferentiated type of sinus epithelium. In the 180 mm. foetus these
 
diverticula are still lined by the undifferentiated epithelium, though the dorso-
 
lateral bays themselves are occupied by an epithelium very similar to that of the
 
vagina. The diverticula are presumably associated with the relative downgrowth of
 
the lower end of the vagina, as has already been pointed out. They are, however,
 
506 D. Bulmer
 
  
very similar to the ‘Wolffian remnant’ described by Bloomfield & Frazer (1927), in
 
a 170 mm. foetus of their collection, but their lining epithelium leaves no doubt of
 
their origin (Pl. 3, fig. 16).
 
  
An interesting viewpoint on the development of the vagina was suggested by
+
Unfortunately, Koff showed no microphotograph of the epithelial distinction between the components of his primitive vaginal plate, but the criterion which he used for the identification of the sinus epithelium was its differentiation into external darkly staining and internal pale-staining zones. It has been noticed in the series of foetuses described here that after the 94 mm. stage the internal cells in the cranial part of the sinus upgrowth are much less pale-staining than they are further caudally. For instance, in the 16% week foetus the large, markedly pale-staining cells are restricted to the enlarged portion of the dorsal wall of the sinus and to the swellings at the caudal end of the sinus upgrowth. Indeed, Koff seems to have identified the two laterally placed swellings with the sino-vaginal bulbs themselves—a conclusion which is difficult to follow and for which there is no evidence in the material described here. The epithelium at the cranial end of the sinus upgrowth is of the same essential character as that further caudally. There is no evidence of any sharp histological distinction in the vaginal mass except the one which has been identified as the junction of the cranial end of the sinus upgrowth with the caudal end of the Miillerian tissue. Koff’s description offers no explanation for the very marked distinction between the two, occurring about half-way up the ‘vagina’ in the 16.5 week foetus.
Zuckerman (1940), who believed that any epithelium of the adult genital tract which
 
responded to oestrogenic stimulation by a stratified squamous proliferation—a
 
‘squamous response ’—was a derivative of the sinus epithelium of the foetus. The
 
conclusion of this present investigation, that the entire vaginal epithelium is derived
 
from the sinus upgrowth, might appear to support Zuckerman’s hypothesis. There
 
is, however, a considerable body of embryological evidence which indicates that in
 
many other mammalian forms the upper vaginal segment, though it is lined by a
 
stratified squamous epithelium and gives a squamous response to oestrogenic
 
stimulation, is a Miillerian derivative. Thus, it seems likely that when the Miillerian
 
epithelium does persist in the vagina it tends to be of stratified squamous form and
 
its response to oestrogenic stimulation squamous in type. Of some interest in this
 
respect is the lining of the ‘ vaginal ’ portion of the utero-vaginal canal in the human
 
foetus by a stratified squamous epithelium of Miillerian origin, and the disappearance
 
of this epithelium after the 140 mm. stage, when it is displaced into the cervical
 
canal. In the absence of any firm knowledge of the hormonal conditions in female
 
human foetuses, we do not know how this stratified Miillerian epithelium responds
 
to oestrogenic stimulation. Probably, however, there is some controlling factor,
 
producing its effect in foetal life in the human subject and throughout life in many
 
other mammals, which stimulates Miillerian cells in the vagina, but not in the
 
uterus, to form a stratified squamous epithelium.
 
  
One of the most interesting problems is that of the extent to which the develop-
 
ment of the human vagina is influenced by hormonal factors. It is a reasonable
 
supposition that the enormous activity of the vaginal epithelium in the older
 
foetuses is a result of stimulation by maternal oestrogens, as Fraenkel & Papanicolou
 
(1938) suggested. The gross differences between the vaginal epithelium in these
 
foetuses and that of the 1-month old infant imply that this oestrogenic stimulation
 
must extend over a considerable period of foetal life—at any rate from the 112 mm.
 
stage onwards. The question of the hormonal control of genital development has
 
introduced a new field of experimental embryology, in which a very large amount
 
of work has already been carried out (for bibliography see J 0st, 1948), and it raises
 
many interesting problems concerning the development of the human vagina. It
 
may be that the enormous enlargement of the lower end of the vaginal mass at the
 
140 mm. stage, associated with the formation of the hymen, is a result of hormonal
 
stimulation to which only the differentiated type of sinus epithelium is sensitive.
 
At an earlier stage, the extension of the sinus upgrowth itself may be due to a
 
similar selective response of the differentiated epithelium. Some of the marked
 
differences between vaginal development in man and in other mammals may result
 
from differences in the degree of hormonal stimulation at various critical periods of
 
foetal life, rather than from inherent differences in the structures which go to form
 
the vagina. On the other hand, the histological differentiation of the epithelium of
 
the sinus upgrowth in the human foetus may be associated with an increased
 
sensitivity to hormonal stimulation, compared with other mammalian forms. While
 
The development of the human vagina 507
 
  
such suggestions can be only tentative, it is, nevertheless, very likely that the
+
The most likely explanation for the histological differences between the cranial and caudal ends of the sinus upgrowth is that the differentiation of its cells progresses from below upwards. Thus, the cells of the caudal end of the upgrowth in the 112 mm. and 16:} week foetuses, when the internal cells are larger, their nuclei smaller and the cell walls deeply stained with eosin, are similar to those occupying the whole of the lower half of the vagina in the 140 mm. foetus. The transversely elongated plate of the vagina appears to differentiate, at each particular stage, by first enlarging to form swellings. The epithelium correspondingly proliferates and the internal cells become large, with small nuclei and deeply stained cell walls. The swellings become still larger, and confluent with each other, the central cells then desquamating to form the vaginal lumen. The 140 mm. foetus shows later and later stages of this process as the sinus upgrowth is followed further and further caudally. The vaginal epithelium continues to proliferate, presumably under the influence of hormonal stimulation, and it is interesting to compare its structure in the two older foetuses with the adult vaginal epithelium as described by Papanicolou, Traut & Marchetti (1948), and more particularly, in view of the probable hormonal influences at work, with the vaginal epithelium of the pregnant woman, described by Smith & Brunner (1934).
endocrinology of vaginal development holds the key to many of these outstanding
 
problems.
 
  
SUMMARY
 
  
1. The development of the human vagina has been studied from a series of female
+
As indicated above, many earlier workers have denied the participation of sinus epithelium in the formation of the vagina. Berry Hart (1896, 1901 and 1911) and Mijsberg (1924) described a contribution to the vagina from the ‘Wolflian bulbs’, proliferations of the epithelium of the lower ends of the Wolffian ducts. There seems no doubt that the Wolifian bulbs were the dorso-lateral projections, and there is no evidence that these latter arise from Wolflian epithelium. Their cells are unlike the cubical Wolffian cells which lie dorsal to them, and much more closely resemble those of the dorsal sinus wall. Berry Hart believed that the epithelium of the Wolffian bulbs extended throughout the entire vagina, while Mijsberg, in a sense less correctly, restricted the Wolffian contribution to a lower vaginal segment. His reasons for this were similar to those which influenced Koff to believe that the sino-vaginal bulbs formed only the lower end of the vagina.
foetuses ranging from 28 to 375 mm. crown-rump length, and from a 1-month old
 
  
infant.
 
  
2. An upgrowth arises from an area of ‘differentiated’ epithelium in the dorsal
+
Other authors have held to the view that the human vagina is entirely derived from the Miillerian utero-vaginal canal. Bloomfield & Frazer (1927) illustrated a section rather similar to the ones shown in P1. 1, figs. 4, 5 and 6, for the 65 mm. foetus, but their interpretation was very different, as they believed that the pale-staining cells in the dorsal sinus wall were the Miillerian cells breaking through into the sinus at the Miillerian tubercle. It is clear that the findings in the 65 mm. foetus make such a view untenable, and this misinterpretation presumably led Bloomfield & Frazer to think that the whole extent of the differentiated type of sinus epithelium was of Miillerian origin.
Wall of the sinus, in a manner which might be said to combine the descriptions of
 
Vilas (1932) and Koff (1933).
 
  
3. The sinus upgrowth extends throughout the entire region of the vagina by the
 
140 mm. stage, and forms the Whole of its epithelial lining. The changes in the
 
  
vaginal epithelium of older foetuses are also described.
+
While the sinus origin of the vaginal epithelium appears to be established, one or two points of detail merit further consideration. From the earliest stage examined, represented by the 28 mm. foetus, the epithelium which lines the part of the sinus from which the sinus upgrowth later arises differs from that of the rest of the pars pelvina in consisting of two cellular zones——darkly staining cells deeply and pale-staining cells superficially. So far, it has been tacitly assumed that both these cell types are of sinus origin, but other workers have placed different interpretations upon them. Vilas (1932) believed that the darkly staining cells were of sinus origin, but was prepared to accept that the pale-staining cells were Wolffian, growing ventrally and medially in the dorsal wall of the sinus to form the ventrally projecting Wolflsche Kamm, identified by Kempermann (1931) and evident in the 65 mm. foetus of this present investigation. Kempermann (1935) also believed that the pale-staining cells were Wolffian in origin, but that they later completely disappeared. The pale-staining cells in the internal layers of the sinus upgrowth at a stage such as that represented by the 94 mm. foetus of this collection were not the Wolffian cells, but a new generation of cells derived from the sinus. Meyer (1934-38), however, believed that the pale-staining Wolffian cells did persist into later foetal life, identifying them with the large pale-staining cells such as occur at the root of the sinus upgrowth in the 112 mm. and 16.5 week foetuses.
  
4. The findings are discussed in relation to the question of an early ingrowth of
 
Wolffian epithelium into the dorsal wall of the sinus, the problem of the behaviour
 
of the lower ends of the Wolffian ducts in female foetuses, and recent opinions on
 
the significance of the sex hormones in genital development.
 
  
My thanks are due to Prof. J. D. Boyd, for the loan of most of the material which
+
This question does not seem possible of solution by ordinary histological methods. Nevertheless, the pale-staining cells in the dorsal wall of the sinus from the 28 mm. stage onwards bear no obvious similarity to the cubical cells which line the Wolffian ducts, and are distinct from the Wolffian cells which lie dorsal to them. It appears just as reasonable to suppose that the pale-staining cells are derivatives of the darkly staining basal cells, and that there is no incorporation of Wolffian cells in the dorsal wall of the sinus at this stage. No such ingrowth occurs in other mammals, and it seems unnecessary to postulate it in the human foetus. Nevertheless, it must be admitted that the differentiation of the sinus epithelium from which the sinus upgrowth arises is a remarkable feature, and it too has not been described in other mammals.
I was able to study. I am also indebted to Messrs J. F. Crane and A. Cain for the
 
microphotographs, and to Mr W. Cruickshank for his assistance with the diagrams.
 
  
REFERENCES
 
  
ACKEREN, F. VAN (1889). Beitrage zur Entwicklungsgeschichte der weiblichen Sexualorgane des
+
Also of some significance is the problem of the behaviour of the lower ends of the Wolifian ducts during the development of the vagina. Descriptions of the lower ends of the Wolffian ducts in female foetuses fall generally into two main categories. In the first are those which maintain that the Wolffian ducts continue to open into the sinus at their original site, immediately lateral to the position of the Miillerian tubercle. Thus, Meyer (1909) described the persistence of the lower ends of the Wolflian ducts in a large number of older foetuses and new-born children, running into the substance of the hymen and opening into the vestibule close beside the hymeneal orifice. On the other hand, many other workers (Tourneux & Legay, 1884; van Ackeren, 1889; Mijsberg, 1924; Koff, 1933) have described the cranial migration of the lower ends of the Wolffian ducts to join the lower end of the vagina itself, though the ducts degenerated very soon after and did not persist into late foetal life.
Menschen. Z. wiss. Zool. 48, 1-46.
 
  
BANKS, W. M. (1864). On the Wolfiian Bodies of the Foetus. Edinburgh.
 
  
BLOOMFIELD, A. & FRAZER, J. E. (1927). The development of the lower end of the vagina. J. Anat.,
+
At first sight, the present investigation supports this latter view. In the 94 mm. foetus the lower end of the left Wolffian duct joins the sinus upgrowth, indicating that the dorso-lateral projection has carried the Wolffian remnant with it as it grew cranially, while in none of the older foetuses was there any trace of the lower ends of the Wolffian ducts. Nevertheless, this evidence is insufficient to suggest that the lower ends of the Wolffian ducts never maintain their openings into the sinus beside the original site of the Miillerian tubercle, particularly in view of the large number of such cases described by Meyer (1909). At that time Meyer regarded these Wolffian remnants as indicative of the entirely Miillerian origin of the vagina, but in his later publications (1934-38) pointed out that they were equally in accord with the account of vaginal development given by Vilas. The Wolffian ducts were not involved in the proliferation which Vilas believed to form the epithelial plate of the vagina, and were therefore left behind near the hymen. Nevertheless, the structures which Meyer now identified as persistent Wolffian remnants do not appear to occupy the same site as those which he had described earlier, but join the lower end of the vagina on the upper aspect of the hymen. In other words, they have been carried cranially for a short distance during the formation of the sinus upgrowth.
Lond., 62, 9-32.
 
  
BOLK, L. (1907). Beitrage zur Affenanatomie VI. Zur Entwicklung und vergleichenden Anatomic
 
des Tractus urethro-vaginalis der Primaten. Z. Morph. Anthr. 10, 250-316.
 
  
BULMER, D. (1955). The Development of the Vagina. Thesis for the degree of M.D., University of
+
It may be that in some instances the lower ends of the Wolffian ducts are not carried cranially with the sinus upgrowth to such a great extent as they have been in the 94 mm. foetus, or indeed that they are not carried cranially at all. This may be because the dorso-lateral projections do not play such a large part in the formation of the sinus upgrowth in these cases, or because the manner of their growth is such as not to involve the lower ends of the Wolffian ducts. In other words, it is possible, as von Lippmann suggested (1939), though with rather a different purpose, that there is some variability in the behaviour of the lower ends of the Wolffian ducts during the early stages of vaginal development. This is supported by the fact that an ectopic ureter, presumably opening by a persistent Wolffian remnant, may join either the vagina or the vestibule (Kermauner, 1909). It is also possible that many of the structures which have been identified as persistent Wolffian remnants were, in fact, not so. In the 140 mm. foetus the dorso-lateral sinus bays end above by sending short diverticula upwards on either side of the lower end of the vagina, lined by the undifferentiated type of sinus epithelium. In the 180 mm. foetus these diverticula are still lined by the undifferentiated epithelium, though the dorso-lateral bays themselves are occupied by an epithelium very similar to that of the vagina. The diverticula are presumably associated with the relative downgrowth of the lower end of the vagina, as has already been pointed out. They are, however, very similar to the ‘Wolffian remnant’ described by Bloomfield & Frazer (1927), in a 170 mm. foetus of their collection, but their lining epithelium leaves no doubt of their origin (Pl. 3, fig. 16).
Cambridge.
 
  
BULMER, D. (1956). The early stages of vaginal development in the sheep. J. Anat., Lond., 90,
 
123-134.
 
  
FELIX W. (1912). The development of the urogenital organs. In Keibel and Mall, Manual of
+
An interesting viewpoint on the development of the vagina was suggested by Zuckerman (1940), who believed that any epithelium of the adult genital tract which responded to oestrogenic stimulation by a stratified squamous proliferation—a ‘squamous response ’—was a derivative of the sinus epithelium of the foetus. The conclusion of this present investigation, that the entire vaginal epithelium is derived from the sinus upgrowth, might appear to support Zuckerman’s hypothesis. There is, however, a considerable body of embryological evidence which indicates that in many other mammalian forms the upper vaginal segment, though it is lined by a stratified squamous epithelium and gives a squamous response to oestrogenic stimulation, is a Miillerian derivative. Thus, it seems likely that when the Miillerian epithelium does persist in the vagina it tends to be of stratified squamous form and its response to oestrogenic stimulation squamous in type. Of some interest in this respect is the lining of the ‘ vaginal ’ portion of the utero-vaginal canal in the human foetus by a stratified squamous epithelium of Miillerian origin, and the disappearance of this epithelium after the 140 mm. stage, when it is displaced into the cervical canal. In the absence of any firm knowledge of the hormonal conditions in female human foetuses, we do not know how this stratified Miillerian epithelium responds to oestrogenic stimulation. Probably, however, there is some controlling factor, producing its effect in foetal life in the human subject and throughout life in many other mammals, which stimulates Miillerian cells in the vagina, but not in the uterus, to form a stratified squamous epithelium.
Human Embryology, Vol. II, p. 752. Philadelphia and London.
 
  
FRAENKEL, L. & PAPANICOLOU, G. N. (1938). Growth, desquamation and involution of the
 
vaginal epithelium of human foetuses and children, with a consideration of the related
 
hormonal factors. Amer. J. Anat. 62, 427-451.
 
  
GOMORI, G. (1952). Microscopic Histochemistry. University of Chicago Press.
+
One of the most interesting problems is that of the extent to which the development of the human vagina is influenced by hormonal factors. It is a reasonable supposition that the enormous activity of the vaginal epithelium in the older foetuses is a result of stimulation by maternal oestrogens, as Fraenkel & Papanicolou (1938) suggested. The gross differences between the vaginal epithelium in these foetuses and that of the 1-month old infant imply that this oestrogenic stimulation must extend over a considerable period of foetal life—at any rate from the 112 mm. stage onwards. The question of the hormonal control of genital development has introduced a new field of experimental embryology, in which a very large amount of work has already been carried out (for bibliography see J 0st, 1948), and it raises many interesting problems concerning the development of the human vagina. It may be that the enormous enlargement of the lower end of the vaginal mass at the 140 mm. stage, associated with the formation of the hymen, is a result of hormonal stimulation to which only the differentiated type of sinus epithelium is sensitive. At an earlier stage, the extension of the sinus upgrowth itself may be due to a similar selective response of the differentiated epithelium. Some of the marked differences between vaginal development in man and in other mammals may result from differences in the degree of hormonal stimulation at various critical periods of foetal life, rather than from inherent differences in the structures which go to form the vagina. On the other hand, the histological differentiation of the epithelium of the sinus upgrowth in the human foetus may be associated with an increased sensitivity to hormonal stimulation, compared with other mammalian forms. While such suggestions can be only tentative, it is, nevertheless, very likely that the endocrinology of vaginal development holds the key to many of these outstanding problems.
  
HART, D. B. (1896). Preliminary note on the development of the clitoris, vagina and hymen.
+
==Summary==
J. Anat., Lond., 31, 18-28.
 
  
HART, D. B. (1901). Morphology of the human urogenital tract. J. Anat., Lond., 35, 330-375.
+
# The development of the human vagina has been studied from a series of female foetuses ranging from 28 to 375 mm. crown-rump length, and from a 1-month old infant.
 +
# An upgrowth arises from an area of ‘differentiated’ epithelium in the dorsal Wall of the sinus, in a manner which might be said to combine the descriptions of Vilas (1932) and Koff (1933).
 +
# The sinus upgrowth extends throughout the entire region of the vagina by the 140 mm. stage, and forms the Whole of its epithelial lining. The changes in the vaginal epithelium of older foetuses are also described.
 +
# The findings are discussed in relation to the question of an early ingrowth of Wolffian epithelium into the dorsal wall of the sinus, the problem of the behaviour of the lower ends of the Wolffian ducts in female foetuses, and recent opinions on the significance of the sex hormones in genital development.
  
HART, D. B. (1911). Adenoma vaginae diffusum (adenomatosis vaginae), with a critical discussion
 
of present views of vaginal and hymeneal development. ‘Edinb. med. J. 6, 577-590.
 
  
HUNTER, R. H. (1930). Observations on the development of the human female genital tract.
+
My thanks are due to Prof. J. D. Boyd, for the loan of most of the material which I was able to study. I am also indebted to Messrs J. F. Crane and A. Cain for the microphotographs, and to Mr W. Cruickshank for his assistance with the diagrams.
Contr. Embryol. Carneg. Inst. 22, 91-108.
 
  
J os'r, A. (1948). Le controle hormonal de la différenciation du sexe. Biol. Rev. 23, 201-236.
+
==References==
  
KEMPERMANN, C. T. (1931). Beitrag zur Frage der Genese der menschlichen vagina. Gegenbaurs
+
ACKEREN, F. VAN (1889). Beitrage zur Entwicklungsgeschichte der weiblichen Sexualorgane des Menschen. Z. wiss. Zool. 48, 1-46.
Jb. 66, 485-531. A
 
508 D. Bulmer
 
  
KEMPERMANN, C. T. (1935). Beitrage zur Entwicklung des Genitaltraktus der Sanger. III. Das
+
BANKS, W. M. (1864). On the Wolfiian Bodies of the Foetus. Edinburgh.
Schicksal der kaudalen Enden der Wolffsche Gange beim Weibe und ihre Bedeutung fiir die
 
Genese der Vagina. Gegenbaurs Jb. 75, 151-179.
 
  
KERMAUNER, F. (1909). Die Missbildungen der weiblichen Geschlechts-organe. In Schwalbe,
+
BLOOMFIELD, A. & FRAZER, J. E. (1927). The development of the lower end of the vagina. J. Anat., Lond., 62, 9-32.
Die Morphologie der Missbildungen des Menschen und der Tiere, Jena. T. III, p. 253.
 
  
KOFF, A. (1933). Development of the vagina in the human foetus. Contr. Embryol. Cizmeg. Instn,
+
BOLK, L. (1907). Beitrage zur Affenanatomie VI. Zur Entwicklung und vergleichenden Anatomic des Tractus urethro-vaginalis der Primaten. Z. Morph. Anthr. 10, 250-316.
24, 59-91.
 
  
LIPPMANN, R. VON (1939). Beitrag zur Entwicklungsgeschichte der menschlichen Vagina und des
+
BULMER, D. (1955). The Development of the Vagina. Thesis for the degree of M.D., University of Cambridge.
Hymen. Z. Anat. EntwGesch. 110, 264-300.
 
  
MEYER, R. (1909). Zur Kentniss des Gartnerschen (oder Wolffschen) Ganges besonders in der
+
BULMER, D. (1956). The early stages of vaginal development in the sheep. J. Anat., Lond., 90, 123-134.
Vagina und dem Hymen des Menschen. Arch. mikr. Anat. 73, 751-792.
 
  
MEYER, R. (1934-1938). Zur Frage der Entwicklung der menschlichen Vagina. I. Arch. Gynaek.
+
FELIX W. (1912). The development of the urogenital organs. In Keibel and Mall, Manual of Human Embryology, Vol. II, p. 752. Philadelphia and London.
158, 639-738; II, Arch. Gynaelc. 163, 205-308; III, Arch. Gynaek. 164, 207-357; IV, Arch.
 
Gynaelc. 165, 504-590; V, Arch. Gynaelc. 167, 306-338.
 
  
MIJSBERG, W. A. (1924). Uber die Entwicklung der Vagina, des Hymen und des Sinus urogenitalis
+
FRAENKEL, L. & PAPANICOLOU, G. N. (1938). Growth, desquamation and involution of the vaginal epithelium of human foetuses and children, with a consideration of the related hormonal factors. Amer. J. Anat. 62, 427-451.
beim Menschen. Z. Anat. EntwGesch. 74, 684-760.
 
  
Mt'iLLER, J . (1830). Bildungsgeschichte der Genitalien. Dusseldorf: Arnz.
+
GOMORI, G. (1952). Microscopic Histochemistry. University of Chicago Press.
  
PAPANICOLOU, G. N., TRAUT, H. F. & MARCHETTI, A. A. (1948). The Epithelia of Woman’s
+
HART, D. B. (1896). Preliminary note on the development of the clitoris, vagina and hymen. J. Anat., Lond., 31, 18-28.
Reproductive Organs. Commonwealth Fund, New York.
 
  
POLITZER, G. (1952). Das Schicksal des Sinus urogenitalis beim Weibe. Z. mikr-anat. Forsch. 59,
+
HART, D. B. (1901). Morphology of the human urogenital tract. J. Anat., Lond., 35, 330-375.
6-28.
 
  
POLITZER, G. (1955). Zur normalen und abnormen Entwicklung der menschlichen Scheide. Anat.
+
HART, D. B. (1911). Adenoma vaginae diffusum (adenomatosis vaginae), with a critical discussion of present views of vaginal and hymeneal development. ‘Edinb. med. J. 6, 577-590.
Am. 102, 271-278. _ ‘
 
  
RATHKE, H. (1832). Abhandlungen zur Bz'ldungs- und Entwrlclclungsgeschichte des Menschen und der
+
HUNTER, R. H. (1930). Observations on the development of the human female genital tract. Contr. Embryol. Carneg. Inst. 22, 91-108.
Thiere. Leipzig. 1
 
  
RETTERER, E. (1891). Sur l’origine du Vagin de la femme. C'.R. Soc. Biol., Paris, Ser. 9, 3, 291-293.
+
J os'r, A. (1948). Le controle hormonal de la différenciation du sexe. Biol. Rev. 23, 201-236.
  
SMITH, B. G. & BRUNNER, E. K. (1934). The structure of the human vaginal mucosa in relation to
+
KEMPERMANN, C. T. (1931). Beitrag zur Frage der Genese der menschlichen vagina. Gegenbaurs Jb. 66, 485-531. A 508 D. Bulmer
the menstrual cycle and to pregnancy. Amer. J . Anat. 54, 27-85.
 
  
SPULER, A. (1930). Entwiclclungsgeschichte des weiblichen Genitalapparates. In Veit-Stoeckel,
+
KEMPERMANN, C. T. (1935). Beitrage zur Entwicklung des Genitaltraktus der Sanger. III. Das Schicksal der kaudalen Enden der Wolffsche Gange beim Weibe und ihre Bedeutung fiir die Genese der Vagina. Gegenbaurs Jb. 75, 151-179.
Handbuch der Gyniikologie, 3rd ed., Band I, p. 470 (quoted by Vilas). Wiesbaden.
 
  
TOURNEUX, F. & LEGAY, C. (1884). Mémoire sur le développement de l’uterus et du vagin. J . Anat.
+
KERMAUNER, F. (1909). Die Missbildungen der weiblichen Geschlechts-organe. In Schwalbe, Die Morphologie der Missbildungen des Menschen und der Tiere, Jena. T. III, p. 253.
Paris, 20, 330-386.
 
  
VALENTIN, G. G. (1835). Handbuch der Entwicklungsgeschichte des Menschen. Berlin.
+
{{Ref-Koff1933}}
  
VILAS, E. (1932). Uber die Entwicklung der menschlichen Scheide. Z. Anat. EntwG'esch. 98,
+
LIPPMANN, R. VON (1939). Beitrag zur Entwicklungsgeschichte der menschlichen Vagina und des Hymen. Z. Anat. EntwGesch. 110, 264-300.
263-292.
 
  
W1sLocK1, G. B., FAWCETT, D. W. & DEMPSEY, E. W. (1951). Staining of stratified squamous
+
MEYER, R. (1909). Zur Kentniss des Gartnerschen (oder Wolffschen) Ganges besonders in der Vagina und dem Hymen des Menschen. Arch. mikr. Anat. 73, 751-792.
epithelium of mucous membranes of Man and Monkey by the periodic acid-Schiff method.
 
Anat. Rec. 110, 359-376.
 
  
ZUCKERMAN, S. (1940). The histogenesis of tissues sensitive to oestrogens. Biol. Rev. 15, 231-271.
+
MEYER, R. (1934-1938). Zur Frage der Entwicklung der menschlichen Vagina. I. Arch. Gynaek. 158, 639-738; II, Arch. Gynaelc. 163, 205-308; III, Arch. Gynaek. 164, 207-357; IV, Arch. Gynaelc. 165, 504-590; V, Arch. Gynaelc. 167, 306-338.
  
EXPLANATION OF PLATES
+
MIJSBERG, W. A. (1924). Uber die Entwicklung der Vagina, des Hymen und des Sinus urogenitalis beim Menschen. Z. Anat. EntwGesch. 74, 684-760.
PLATEI
 
  
Fig. 1. 28 mm. embryo. Transverse section through the openings of the Wolffian ducts into the
+
MULLER, J . (1830). Bildungsgeschichte der Genitalien. Dusseldorf: Arnz.
urogenital sinus. The sinus epithelium consists of basal deeply staining and superficial pale-
 
staining cells, and the pale-staining cells extend for a short distance into the lower ends of the
 
Wolffian ducts. The Miillerian ducts are in close relation with the Wolflian ducts, but a small
 
mass of mesoderm separates them from the sinus. ( x 215.)
 
  
Fig. 2. 48 mm. foetus. Sagittal section through the opening of the right Wolfiian duct. The
+
PAPANICOLOU, G. N., TRAUT, H. F. & MARCHETTI, A. A. (1948). The Epithelia of Woman’s Reproductive Organs. Commonwealth Fund, New York.
differentiation of the sinus epithelium in this region can be seen, and the extension of the
 
pale-staining cells into the lower end of the Wolffian duct. ( x 215.)
 
  
Fig. 3. 65 mm. foetus. Transverse section through the genital cord. The Wolffian ducts are very
+
POLITZER, G. (1952). Das Schicksal des Sinus urogenitalis beim Weibe. Z. mikr-anat. Forsch. 59, 6-28.
small structures, on either side of the utero-vaginal canal. ( x 215.)
 
  
Fig. 4. 65 mm. foetus. Transverse section through the junction of Miillerian and sinus epithelia.
+
POLITZER, G. (1955). Zur normalen und abnormen Entwicklung der menschlichen Scheide. Anat. Am. 102, 271-278.
A mass of darkly staining cells (d), arising from the dorsal wall of the sinus, separates the
 
caudal end of the Miillerian epithelium (m) from the sinus lumen. On the right side the section
 
passes below the bulk of the dorso-lateral projection, and the Wolffian duct is large. On the
 
left the Wolffian duct is a small structure, applied to the dorsal aspect of the dorso-lateral
 
projection (dp). (x 215.) A
 
J ournal of Anatomy, Vol. 91, Part 4
 
  
BULMF.R——Tm-1 DEVELOPMENT 01? THE HUMAN VAGINA
+
RATHKE, H. (1832). Abhandlungen zur Bz'ldungs- und Entwrlclclungsgeschichte des Menschen und der Thiere. Leipzig. 1
(Facing p. 508)
 
I
 
  
BULMER—THE DEVELOPMENT on THE HUMAN VAGINA
+
RETTERER, E. (1891). Sur l’origine du Vagin de la femme. C'.R. Soc. Biol., Paris, Ser. 9, 3, 291-293.
  
4.
+
SMITH, B. G. & BRUNNER, E. K. (1934). The structure of the human vaginal mucosa in relation to the menstrual cycle and to pregnancy. Amer. J . Anat. 54, 27-85.
N
 
a
 
P
 
1.:
 
9
 
d
 
V
 
aw
 
m
 
.m
 
a
 
n
 
A
 
:0!
 
M
 
n
 
T
 
u
 
0
 
J
 
4
 
t
 
T
 
a
 
P
 
L,
 
9
 
l.
 
0
 
V
 
  
J ournal of Anatomy,
+
SPULER, A. (1930). Entwiclclungsgeschichte des weiblichen Genitalapparates. In Veit-Stoeckel, Handbuch der Gyniikologie, 3rd ed., Band I, p. 470 (quoted by Vilas). Wiesbaden.
BULMER—THE DEVELOPMENT OF THE HUMAN VAGINA
 
Fig.
 
  
Fig.
+
TOURNEUX, F. & LEGAY, C. (1884). Mémoire sur le développement de l’uterus et du vagin. J . Anat. Paris, 20, 330-386.
  
Fig.
+
VALENTIN, G. G. (1835). Handbuch der Entwicklungsgeschichte des Menschen. Berlin.
  
Fig.
+
VILAS, E. (1932). Uber die Entwicklung der menschlichen Scheide. Z. Anat. EntwG'esch. 98, 263-292.
  
Fig.
+
W1sLocK1, G. B., FAWCETT, D. W. & DEMPSEY, E. W. (1951). Staining of stratified squamous epithelium of mucous membranes of Man and Monkey by the periodic acid-Schiff method. Anat. Rec. 110, 359-376.
  
Fig.
+
ZUCKERMAN, S. (1940). The histogenesis of tissues sensitive to oestrogens. Biol. Rev. 15, 231-271.
  
Fig.
+
==Explanation Of Plates==
  
Fig.
+
===Plate 1===
 +
[[File:Bulmer1957 plate01.jpg|800px]]
  
Fig.
+
Fig. 1. 28 mm embryo. Transverse section through the openings of the Wolffian ducts into the urogenital sinus. The sinus epithelium consists of basal deeply staining and superficial pale-staining cells, and the pale-staining cells extend for a short distance into the lower ends of the Wolffian ducts. The Miillerian ducts are in close relation with the Wolflian ducts, but a small mass of mesoderm separates them from the sinus. ( x 215.)
  
Fig.
+
Fig. 2. 48 mm foetus. Sagittal section through the opening of the right Wolfiian duct. The differentiation of the sinus epithelium in this region can be seen, and the extension of the pale-staining cells into the lower end of the Wolffian duct. (x 215.)
  
Fig.
+
Fig. 3. 65 mm foetus. Transverse section through the genital cord. The Wolffian ducts are very small structures, on either side of the utero-vaginal canal. ( x 215.)
  
Fig.
+
Fig. 4. 65 mm foetus. Transverse section through the junction of Mullerian and sinus epithelia. A mass of darkly staining cells (d), arising from the dorsal wall of the sinus, separates the caudal end of the Mullerian epithelium (m) from the sinus lumen. On the right side the section passes below the bulk of the dorso-lateral projection, and the Wolffian duct is large. On the left the Wolffian duct is a small structure, applied to the dorsal aspect of the dorso-lateral projection (dp). (x 215.)
  
Fig.
 
Fig.
 
  
Fig.
+
Fig. 5. 65 mm foetus. Transverse section 16 p. caudal to Fig. 4. The Mullerian epithelium now forms a smaller mass dorsally, and a few of the darkly staining sinus cells separate it from the pale-staining sinus epithelium ventrally. ( x 215.)
  
509
+
Fig. 6. 65 mm foetus. Transverse section 8 ,u caudal to Fig. 5. ( x 215.)
  
5. 65 mm. foetus. Transverse section 16 p. caudal to Fig. 4. The Miillerian epithelium now
 
forms a smaller mass dorsally, and a few of the darkly staining sinus cells separate it from the
 
pale-staining sinus epithelium ventrally. ( x 215.)
 
  
6. 65 mm. foetus. Transverse section 8 ,u caudal to Fig. 5. ( x 215.)
+
===Plate 2===
  
The development of the human vagina
+
Fig. 7. 94 mm. foetus. Coronal section through the cranial and dorsal enlargement of the sinus which forms the root of the sinus upgrowth. The epithelial differentiation is very weH marked. ( x 84.)
  
PLATE 2
+
Fig. 8. 94 mm. foetus. Coronal section through the sinus upgrowth, 90 ,u. dorsal to Fig. 7. The small darkly staining cells in the centre of the section (m) represent the caudal tip of the Mullerian epithelium. A thin layer of darkly staining cells forms the outer layer of the sinus upgrowth, and there is a small mass of these cells on the right (to the left of the photograph). 90 /1. further dorsally, a similar small mass, on the other side, is joined by the persistent lower end of the left Wolffian duct. ( x 215.)
  
7. 94 mm. foetus. Coronal section through the cranial and dorsal enlargement of the sinus
+
Fig. 9. 112 mm. foetus. Transverse section through the dorsal part of the sinus, showing the two roots of the sinus upgrowth separated from each other by the mesodermal septum (ms). The pale-staining internal cells of the sinus are very prominent. ( x 215.)  
which forms the root of the sinus upgrowth. The epithelial differentiation is very weH marked.
 
( x 84.)
 
  
8. 94 mm. foetus. Coronal section through the sinus upgrowth, 90 ,u. dorsal to Fig. 7. The
+
Fig. 10. 112 mm. foetus. Transverse section through the vaginal mass, 288 /1. cranial to Fig. 9. The sinus upgrowth forms two lateral wings, while the central portion (m) is formed by the paler-staining polygonal cells of the caudal end of the Miillerian tissue. ( x 215.)
small darkly staining cells in the centre of the section (m) represent the caudal tip of the
 
Miillerian epithelium. A thin layer of darkly staining cells forms the outer layer of the sinus
 
upgrowth, and there is a small mass of these cells on the right (to the left of the photograph).
 
90 /1. further dorsally, a similar small mass, on the other side, is joined by the persistent lower
 
end of the left Wolffian duct. ( x 215.)
 
  
9. 112 mm. foetus. Transverse section through the dorsal part of the sinus, showing the two
+
Fig. 11. 16.5 week foetus. Transverse section through the junction of the Miillerian epithelium of the utero-vaginal canal (m) with the cranial wing of the sinus upgrowth on the left side. ( x 215.)
roots of the sinus upgrowth separated from each other by the mesodermal septum (ms).
 
The pale-staining internal cells of the sinus are very prominent. ( x 215.) '
 
10. 112 mm. foetus. Transverse section through the vaginal mass, 288 /1. cranial to Fig. 9.
 
The sinus upgrowth forms two lateral wings, while the central portion (m) is formed by the
 
paler-staining polygonal cells of the caudal end of the Miillerian tissue. ( x 215.)
 
  
11. 161} week foetus. Transverse section through the junction of the Miillerian epithelium of
+
Fig. 12. 16.5 week foetus. Transverse section through the sinus showing the junction of its dorsal wall with the caudal end of the sinus upgrowth. The central enlargement of the upgrowth is immediately dorsal to the sinus lumen, and a further enlargement projects dorsally from it. The large clear-staining internal cells are prominent in the central enlargement. In the dorsal enlargement the cytoplasm and cell boundaries of the internal cells are markedly eosinophilic. ( x 84.)
the utero-vaginal canal (m) with the cranial wing of the sinus upgrowth on the left side.
 
( x 215.)
 
  
12. 161} week foetus. Transverse section through the sinus showing the junction of its dorsal
+
Fig. 13. 140 mm. foetus. Transverse section through the left side of the cervical canal, showing the junction between the stratified Miillerian epithelium (m) and the cranial tip of the sinus upgrowth. ( x 160.)
wall with the caudal end of the sinus upgrowth. The central enlargement of the upgrowth is
 
immediately dorsal to the sinus lumen, and a further enlargement projects dorsally from it.
 
The large clear-staining internal cells are prominent in the central enlargement. In the
 
dorsal enlargement the cytoplasm and cell boundaries of the internal cells are markedly
 
eosinophilic. ( x 84.)
 
  
13. 140 mm. foetus. Transverse section through the left side of the cervical canal, showing the
+
===Plate 3===
junction between the stratified Miillerian epithelium (m) and the cranial tip of the sinus
 
upgrowth. ( x 160.)
 
  
PLATE 3
+
Fig. 14. 140 mm. foetus. Transverse section through the left vaginal enlargement, just below the middle of the cranio-caudal extent of the vagina. The internal cells are large, their nuclei relatively small and the cell-boundaries markedly eosinophilic. ( x 215.)
  
. 14. 140 mm. foetus. Transverse section through the left vaginal enlargement, just below the
+
Fig. 15. 140 mm. foetus. Transverse section through the urogenital sinus and the lower end of the vagina, at the level of the paired hymeneal orifices. On each side of the ventro-lateral aspect of the vagina is the small cranial extremity of the dorso-lateral sinus bay (db). ( x 30.)
  
middle of the cranio-caudal extent of the vagina. The internal cells are large, their nuclei
+
Fig. 16. 140 mm. foetus. Transverse section through the wall of the dorso-lateral sinus bay, showing its lining of undifferentiated sinus epithelium. ( X 450.)
relatively small and the cell-boundaries markedly eosinophilic. ( x 215.)
 
  
. 15. 140 mm. foetus. Transverse section through the urogenital sinus and the lower end of the
+
Fig. 17. 140 mm. foetus. Transverse section through the lower portion of the hymen, showing the vaginal epithelium above, separated by the hymeneal connective tissue from the undifferentiated sinus epithelium below. ( x 450.)
  
vagina, at the level of the paired hymeneal orifices. On each side of the ventro-lateral aspect
+
Fig. 18. 180 mm. foetus. Transverse section through the junction of the vaginal epithelium with the colunmar epithelium of the cervix. ( x 120.)
of the vagina is the small cranial extremity of the dorso-lateral sinus bay (db). ( x 30.)
 
  
16. 140 mm. foetus. Transverse section through the wall of the dorso-lateral sinus bay,
+
Fig. 19. 180 mm. foetus. Section through the vaginal epithelium. ( x 280.)
showing its lining of undifferentiated sinus epithelium. ( X 450.)
 
  
17. 140 mm. foetus. Transverse section through the lower portion of the hymen, showing the
+
Fig. 20. 375 mm. foetus. Section of the vaginal epithelium overlying a mesodermal papilla. ( x 280.)
vaginal epithelium above, separated by the hymeneal connective tissue from the undiflerenti-
 
ated sinus epithelium below. ( x 450.)
 
  
18. 180 mm. foetus. Transverse section through the junction of the vaginal epithelium with
+
Fig. 21. Vaginal epithelium in the 1-month old infant. The epithelium is not of uniform thickness, and this photograph is taken from an area where it is rather thicker than usual, in order to give a better impression of its histological structure. (x 320.)
the colunmar epithelium of the cervix. ( x 120.)
 
  
19. 180 mm. foetus. Section through the vaginal epithelium. ( x 280.)
 
  
20. 375 mm. foetus. Section of the vaginal epithelium overlying a mesodermal papilla.
+
{{Footer}}
( x 280.)
 
  
21. Vaginal epithelium in the 1-month oldinfant. The epithelium is not of uniform thickness,
+
[[Category:Female]][[Category:Vagina]][[Category:Genital]]
and this photograph is taken from an area where it is rather thicker than usual, in order to
+
[[Category:Historic Embryology]][[Category:1950's]][[Category:Draft]]
give a better impression of its histological structure. (x 320.)
 

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Bulmer D. The development of the human vagina. (1957) J. Anat. 91: 490-509.

Online Editor Note 
Mark Hill.jpg
This historic 1957 paper by Bulmer is an early description of female vagina development. Current research suggests that Bulmer's description is more correct and that Koff's (1937).



See also Koff A. Development of the vagina in the human fetus. (1933) Contrib. Embryol., Carnegie Inst. Wash. Publ. 443, 24: 59-60.


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Historic Embryology - Genital 
General: 1901 Urinogenital Tract | 1902 The Uro-Genital System | 1904 Ovary and Testis | 1912 Urinogenital Organ Development | 1914 External Genitalia | 1921 Urogenital Development | 1921 External Genital | 1942 Sex Cords | 1953 Germ Cells | Historic Embryology Papers | Historic Disclaimer
Female: 1904 Ovary and Testis | 1904 Hymen | 1912 Urinogenital Organ Development | 1914 External Genitalia | 1914 Female | 1921 External Genital | 1927 Female Foetus 15 cm | 1927 Vagina | 1932 Postnatal Ovary
Male: 1887-88 Testis | 1904 Ovary and Testis | 1904 Leydig Cells | 1906 Testis vascular | 1909 Prostate | 1912 Prostate | 1914 External Genitalia | 1915 Cowper’s and Bartholin’s Glands | 1920 Wolffian tubules | 1935 Prepuce | 1935 Wolffian Duct | 1942 Sex Cords | 1943 Testes Descent | Historic Embryology Papers | Historic Disclaimer


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The Development Of The Human Vagina

By D. Bulmer

Anatomy Department, University of Aberdeen

Introduction

The literature on the development of the human vagina is already so abundant that this further contribution is made only with some trepidation. However, the findings which form the substance of this paper seem of sufficient significance to be recorded, since they clearly demonstrate a method of vaginal development which has not so far been generally accepted in this country. The material studied, while not always forming as complete a series as might be wished, has in most cases been in excellent condition for detailed histological examination, and it is possible that the previous confusions and disagreements on this subject were largely due to deficiencies in the material available to earlier workers.


Bloomfield & Frazer (1927) pointed out that the descriptions of vaginal development in the literature could be divided into three main groups, depending on the structures which their authors believed to take part in the formation of the vagina, and it will be convenient to employ this classification here.


In the first group are those accounts which have attributed the origin of the entire vagina to the lower end of the Mullerian utero-vaginal canal. This opinion first gained general acceptance from the demonstration by Thiersch and others, work which is well summarized by Banks (1864), of the fusion of the Miillerian ducts in the genital cord, and in this century has been supported by Felix (1912), Bloomfield & Frazer (1927), Hunter (1930) and von Lippmann (1939). It may be regarded as the ‘ classical’ account of vaginal development, and was for many years the standard textbook description.


The second group consists of those descriptions which supposed that the vaginal epithelium was formed in part (Tourneux & Legay, 1884; Mijsberg, 1924) or in whole (Hart, 1896, 1901 and 1911; Kempermann, 1931) from the lower ends of the Wolffian ducts.


The third group includes the accounts of all those workers who believed that the epithelium of the urogenital sinus made a contribution to the vagina. Before the time of Thiersch it was accepted that the entire vagina was derived from the sinus (Muller, 1830; Rathke, 1832; Valentin, 1835), but this opinion was discarded when the fusion of the Miillerian ducts became known. Retterer (1891), however, suggested that while most of the vagina was formed from the utero-vaginal canal a short lower segment arose by the splitting of the upper part of the sinus into dorsal and ventral channels, and this view was later supported by Bolk (1907). Koff (1933), whose work is recognized by most current British and American textbooks, believed that the lower one-fifth of the vagina was derived from the sinus by the growth of paired epithelial ‘sino-vaginal bulbs’ from the dorsal sinus wall, these bulbs fusing together to form a lower vaginal segment. On the other hand, Spuler (1930), Vilas (1932), Kempermann (1935) and Meyer (1934-38) believed that a proliferation of cells from the dorsal wall of the sinus gave rise to the epithelial lining of the entire vagina, displacing the epithelium of the utero-vaginal canal as far as the cervix. This opinion has recently been supported by Politzer (1955), and Zuckerman (1940) showed that there was a considerable body of endocrinological evidence in its favour.

Material

The material consists of thirteen embryos and foetuses, ranging from 28 to 375 mm. crown—rump length, and an infant of 1 month. The majority of the specimens were already sectioned and stained with haematoxylin and eosin, alternately with haematoxylin and eosin and a trichrome stain, or by the de Castro method of silver impregnation. The remainder were sectioned at 6-10 /1., either transversely or coronally, and the sections stained mainly with haematoxylin and eosin or a trichrome stain. With some of the larger specimens slides were also stained with Best’s ammoniacal carmine and by the periodic acid-Schiff technique (Gomori, 1952)

28 mm Embryo

In the lower part of the genital cord the Miillerian ducts are in apposition with each other, their medial walls forming a septum between the two lumina. They are lined by a closely packed columnar epithelium and lie between the two Wolffian ducts, rather larger structures with a cubical epithelium. The caudal ends of the Miillerian ducts do not quite reach the dorsal wall of the sinus, remaining separated from the Miillerian tubercle by a small mass of mesoderm, but on either side they are in close contact with the lowerends of the Wolffian ducts (Pl. 1, fig. 1).


Most of the pars pelvina of the sinus is lined by an epithelium consisting of three or four layers of small, darkly staining cells with closely arranged nuclei, but in the region of the Miillerian tubercle the epithelium of the dorsal sinus wall is differentiated into a thin basal layer of deeply staining cells overlain by’ one to three layers of larger and very pale staining cells with relatively smaller nuclei. At the Wolffian openings, on either side of the Miillerian tubercle, these pale cells seem to be compressed together, and they extend backwards for a short distance into the lower ends of the Wolffian ducts themselves.

42 mm Foetus

The lower portions of the Miillerian ducts are completely fused together as the utero-vaginal canal and the caudal tip of the Miillerian epithelium forms a solid mass in contact with the dorsal wall of the sinus, though a small central mass of mesoderm interrupts this contact in the midline. On either side of the Miillerian tubercle the Wolffian ducts enter the sinus, and are now of about the same calibre as the utero-vaginal canal. The sinus epithelium presents the same features as in the 28 mm. specimen (Pl. 1, fig. 2).

50 mm Foetus

This specimen shows no significant developmental change, except that the sinus epithelium in the region of the Miillerian tubercle is now considerably thicker. This epithelium, divided into basal deeply staining and superficial pale-staining zones, will in future be referred to as the differentiated type of sinus epithelium. 492 D. Bulmer

65 mm Foetus

The Mullerian utero-vaginal canal is a large structure, oval in cross-section and with its long axis lying transversely (Pl. 1, fig. 3). Throughout most of its extent it is lined by a closely packed columnar epithelium, but about 0-3 mm. above the caudal end the lining cells lose their columnar arrangement and form a thick stratified polygonal epithelium, which at the lowermost tip completely occludes the lumen. The Wolffian ducts are very small structures, lined by a cubical epithelium, and lie on either side of the utero-vaginal canal. There is a short segment where the Wolffian ducts have completely disappeared, just above their lower ends, but they reappear below this to join the dorsal wall of the sinus.


The urogenital sinus shows a very significant advance in the region previously occupied by the Miillerian tubercle (Pl. 1, figs. 4, 5, 6). On either side the Wolffian ducts join ‘dorso-lateral projections’ of the sinus, solid epithelial structures which prevent the communication of the ducts with the sinus lumen and are in contact on their dorso-medial aspects with the solid mass of Miillerian epithelium at the caudal end of the utero-vaginal canal. More medially, the Miillerian epithelium is displaced dorsally by a proliferation of darkly staining cells from the dorsal sinus wall, between the bases of the two dorso-lateral projections (Pl. 1, fig. 4). The dorso-lateral projections are each formed by a central mass" of pale-staining cells, with small nuclei, surrounded by a thin basal layer of more darkly staining cells, and the cubical cell lining of the lower ends of the Wolffian ducts is applied to their dorsal aspects. Caudal and ventral to the proliferation of darkly staining cells from the dorsal sinus wall, the pale-staining cells extend forwards and medially to form a crest projecting into the dorsal aspect of the sinus lumen (Pl. 1, figs. 5, 6)—the structure identified by Kempermann (1931) as the Wolflsche Kamm. Apart from this differentiation in the region previously occupied by the Miillerian tubercle, the remainder of the pars pelvina is lined by a darkly staining stratified epithelium of six or seven layers of small cells.


In this specimen, therefore, the sinus cells in the region which was previously lined by the differentiated type of epithelium form a proliferative zone, apparently composed of three elements. On either side are the dorso-lateral projections, associated with the Wolffian openings, while between them is a proliferation of darkly staining cells from the dorsal sinus wall.

68 mm Foetus

This specimen is at only a slightly later developmental stage than the 65 mm. foetus, but several interesting differences may be noted. The Wolffian ducts are present throughout the whole of the genital cord as small, but easily recognizable structures. The occlusion of the lumen of the caudal portion of the utero-vaginal canal reaches further cranially than in the 65 mm. specimen, to a distance of about 0-3 mm. above the junction of Miillerian and sinus epithelia. A small mesodermal mass is enclosed in the root of ‘the proliferation of darkly staining cells from the dorsal wall of the sinus, splitting it into bilateral elements which meet each other behind the mesodermal mass and are there in contact with the caudal end of the Miillerian epithelium (Text-fig. la).


The most interesting feature is the appearance of a characteristic system of longitudinal folds in the sinus wall (Text-fig. 1), foreshadowed at the 65 mm. stage but now very much more distinct. It may be noted that there is a pronounced fold—termed the ‘ urethro-vaginal fold ’——demarcating from the rest of the sinus its cranial and dorsal portion which forms the zone of contact with the Miillerian tissue. The dorsal margins of the urethro-vaginal folds run from the dorsal wall of the sinus, below the dorso-lateral projections, to meet each other behind the lower end of the urethra, and limit the area, dorsal and cranial to them, which is occupied by the differentiated type of sinus epithelium. The pattern of the folds in the wall of the human sinus has been described previously by Mijsberg (1924) and Politzer (1952). They are indicated in the diagrams in Text-figs. 1-4, and a more detailed account has been given elsewhere (Bulmer, 1955).


Text-fig. 1. 68 mm. foetus. The figure on the left is a graphic reconstruction (x 20) of a median sagittal section through the lower end of the utero-vaginal canal and the urogenital sinus. The figures on the right, a-g, are transverse sections at the levels indicated in the sagittal section. The dorsal aspect of the sections is towards the left. The Miillerian epithelium is shown by the solid black shading, and the sinus epithelium by the stippling. A small area of connective tissue, ct in fig. 1 a, interrupts the sinus proliferation in the midline. The folds of the sinus wall are indicated in the transverse sections, and their relative positions in the sagittal section are shown by the dotted lines. dl, dorso-lateral fold; md, median dorsal fold; l, lateral fold; vl, ventro-lateral fold; uv, urethro-lateral fold ; v, median ventral fold. The dorso-lateral sinus bay lies between the lateral and dorso-lateral folds (figs. 1 f, 1 g) or between the lateral and median dorsal folds (fig. 1e), and is joined at ba by the duct of Bartholin’s gland. The ventro-lateral bay is between the lateral and ventro-lateral folds. It will be noticed that the relief of the sinus wall compares very closely with that described by Mij sberg (1924) and Politzer (1952) at similar developmental stages.

14 week Foetus

The dorso-lateral projections can be identified, similar in structure to those of the 65 mm. stage, and their dorso-medial aspects are in contact with the Miillerian epithelium. Between their bases is the mass of darkly staining cells proliferating from the dorsal wall of the sinus, ventral to the Miillerian epithelium and now more extensive than in the 65 mm. foetus. 494 D. Bulmer

94 mm Foetus

There is a considerable increase in size of the sinus compared with the 68 mm. stage (Text-fig. 2), but the arrangement of the longitudinal folds remains essentially unchanged. The urethro-vaginal fold is a marked feature, accentuated by the enlargement of the sinus which lies dorsal and cranial to it (Text-fig. 2b). This enlargement is associated with a considerable thickening of the epithelium, which now consists of a basal zone of five or six layers of small, darkly staining cells, with relatively large nuclei, clearly demarcated from a superficial zone of three or four layers of larger, clear staining polygonal cells with relatively much smaller nuclei. There is a striking distinction between the two zones in the low-power view (Pl. 2, fig. 7), and this epithelium is markedly different from the much thinner, undifferentiated type of epithelium, of four or five layers of smaller, rather darkly staining cells, which lines the rest of the pars pelvina.



Text-fig. 2. 94 mm. foetus. Median sagittal section through the sinus and the lower end of the vagina, with the corresponding coronal sections ( x 13;). Shading and lettering as for Text-fig. 1. The dotted lines in the sagittal section indicate the relative positions of the folds in the upper part of the sinus wall. The coronal sections, a——i, are shown with their cranial ends (i.e. the ventral wall of the sinus) towards the top.


The enlargement of the sinus behind the urethro-vaginal folds also forms the root of a short ‘sinus upgrowth’, projecting dorsally and cranially from the sinus to meet the caudal end of the Miillerian epithelium. The lower end of the sinus up- growth contains paired lumina, continuous with the sinus lumen, and the epithelium is of the same differentiated type as that of the sinus enlargement. Followed further cranially the lumina disappear, and the sinus upgrowth forms a solid crescentic mass of epithelium in which the basal and superficial zones are still distinct (Pl. 2, fig. 8), though the basal cells are not so prominent as they are more caudally. In addition, a small mass of darkly staining cells, the caudal end of the Miullerian tissue, is embedded in this cranial end of the sinus upgrowth.


As the vaginal mass is followed still further cranially the left side of the sinus upgrowth is joined by a short persistent segment of the lower end of the left Wolffian duct, and the Miillerian epithelium comes to occupy a gradually increasing area in the centre. Eventually, about 240 ,a above the root of the sinus upgrowth, the sinus cells are completely replaced by the solid Miillerian epithelium, which is canalized a short distance above this as the lower end of the utero-vaginal canal. This part of the canal is lined by a three- or four-layered stratified polygonal epithelium, which extends cranially to meet the columnar cell lining of the upper part. The level of junction between these two types of Miillerian epithelium coincides with a fusiform swelling of the genital cord, corresponding with that identified by Koff (1933) as the site of the future cervix.


It can be appreciated that several changes have occurred to reach this stage of development. The three components which formed the proliferation of the sinus from the 65 mm. stage onwards—the two dorso-lateral projections and the darkly staining cells between them—have apparently fused together to form a single mass which extends dorsally and cranially as the sinus upgrowth. The lower ends of the Wolflian ducts have disappeared except for a short persistent segment on the left side, which, as might be expected, joins the side of the sinus upgrowth. In addition, the ‘ vaginal ’ portion of the utero-vaginal canal, so far as this can be defined, is now entirely lined by a stratified polygonal epithelium, presumably derived from the original columnar Mullerian epithelium. One of the most interesting features, however, is the differentiation of the sinus epithelium behind and above the urethro-vaginal folds. A similar differentiation, though less marked, has been noted since the 28 mm. stage, always confined to this particular region of the sinus, and it is from this differentiated type of epithelium that the sinus upgrowth appears to arise.

112 mm Foetus

The configuration of the urogenital sinus shows little change from the 94 mm. stage, though the pars phallica is now becoming more dorso-ventrally elongated, The sinus upgrowth extends for about 570 ,a above the dorsal wall of the sinus, as a transversely elongated epithelial plate, and its cranial end reaches up for a short distance as tapering ‘wings ’ on either side of the lower end of the utero-vaginal canal. Caudally it is continuous with the dorsal wall of the sinus, but its root is split into two by a small mesodermal septum (Pl. 2, fig. 9). Dorsal to this septum the two roots join each other to form the sinus upgrowth, while on its ventral aspect they are continuous with the enlarged dorsal and cranial portion of the sinus which lies above and behind the urethro-vaginal folds. This arrangement obviously cannot have arisen from conditions such as have been described in the 94 mm. foetus. Apparently, as in the 68 mm. specimen, a small mesodermal septum must have divided the root of the sinus upgrowth at the time of its initial formation.


The epithelium of the sinus upgrowth stains rather more deeply than in the 94 mm. foetus, but the basal and superficial zones can be readily recognized and it can be distinguished from the Miillerian epithelium with which it is in contact (Pl. 2, fig. 10). At the caudal end of the upgrowth, and in the enlargement of the dorsal portion of the sinus from which it arises, the epithelium is of the same differentiated type, but here the pale-staining cells are much larger and more prominent than they are further cranially, their cytoplasm eosinophilic and their nuclei very small (Pl. 2, fig. 9). The remainder of the pars pelvina is still lined by the same undifferentiated type of epithelium as in the earlier stages.


The lower part of the utero-vaginal canal is lined by a stratified polygonal epithelium, and the first sign of the differentiation of the surrounding mesoderm which marks the position of the future external os (Bulmer, 1955) indicates that this epithelium lines the entire ‘vaginal ’ portion of the canal, the uterine segment retaining its original columnar epithelium.

16.5 week Foetus

The crown—rump length of this specimen is unfortunately not known, but it shows a slightly later stage of development than the 112 mm. foetus. There is now a marked dorso-ventral elongation of the pars phallica and a relative and absolute shortening of the pars pelvina compared with the 94 mm. foetus. Though this change of shape has slightly modified the relative positions of the folds in the sinus wall their pattern remains essentially the same (Text-fig. 3).


Text-fig. 3. 16.5 week foetus. Median sagittal section and the corresponding transverse sections through the sinus and the lower end of the utero-vaginal canal (x 13;). The arrow at 3 indicates the level of the cranial tips of the sinus upgrowth, on either side of the lower end of the utero-vaginal canal. Other lettering and shading as for Text-fig. 1.


The sinus upgrowth extends cranially for a distance of about 1-6 mm. — approximately half the extent of the future vagina as indicated by the site of the external os. In most of its extent the upgrowth forms a solid transversely elongated epithelial plate, and cranially it extends for a short distance as bilateral wings on either side of the lower end of the utero-vaginal canal. Its epithelium is again diiferentiated into basal and superficial zones, and the thickness of section (12 ,u) seems to accentuate the distinction between Miillerian and sinus epithelia (Pl. 2, fig. 11). The ‘vaginal’ portion of the utero-vaginal canal is lined by a four- or five-layered Stratified Miillerian epithelium, and the superficial cells are now becoming more flattened.


At its caudal end the sinus upgrowth joins the enlargement of the sinus which lies cranial and dorsal to the urethro-vaginal folds, unsplit by any mesodermal septum, and this lower end of the upgrowth now shows three swellings of its epithelial plate, one centrally and one on either side. In these swellings, and in the dorsal enlargement of the sinus, the epithelium is rather different from that in the cranial part of the sinus upgrowth. The internal cells are larger and the nuclei smaller, so that the distinction between basal and superficial zones is much more apparent (Pl. 2, fig. 12). In addition, particularly in the swellings of the sinus upgrowth, the cytoplasm of the internal cells is eosinophilic, and the cell walls deeply stained. The remainder of the pars pelvina, below and ventral to the urethro-vaginal folds, is still lined by an undifferentiated type of epithelium, consisting of four or five layers of small, darkly staining cells.

140 mm Foetus

In this specimen many further developments are apparent. The sinus upgrowth extends to the lower end of the cervical canal as a solid, transversely elongated epithelial plate in which the basal and internal zones of cells can be distinguished. Here it meets a stratified squamous Miillerian epithelium (Pl. 2, fig. 13), which consists of very much smaller cells and lines the lower portion of the cervical canal immediately above the sinus upgrowth, intervening between this and the columnar epithelium of the rest of the uterus above. The vaginal fornices have not yet appeared.


As the sinus upgrowth is followed caudally, it develops, about the middle of its cranio-caudal extent, enlargements similar to those seen at the lower end of the upgrowth in the 16% week foetus—a large swelling centrally, and smaller swellings at each lateral extremity. Traced further caudally these swellings become larger, until eventually they merge together to form a single mass occupying about the lower one-third of the vagina, rather heart-shaped in cross-section and with a large central lumen (Text-fig. 4). In the swellings the vaginal epithelium consists of a narrow basal zone of darkly staining cells, with relatively large nuclei, and a mass of large internal pale-staining cells with very small nuclei, eosinophilic cytoplasm and very deeply stained cell walls (Pl. 3, fig. 14). In the canalized portion of the vagina the epithelium is very similar, with a thick zone of internal cells of which the superficial layers are flattened. The lumen is filled by a mass of desquamated material, and the PAS technique demonstrates that all but the basal cells of the epithelial lining are loaded with glycogen.


The lower end of the vagina communicates with the sinus by paired hymeneal orifices (Text-fig. 4b and P1. 3, fig. 15), separated from each other by a small median mesodermal septum, and the great enlargement of the lower end of the vagina has resulted in the extension of its area of contact with the sinus, particularly on the lateral and caudal aspects of the orifices (Text-fig. 40). In this way the hymen is formed, consisting of a plate of dense connective tissue, lined above by vaginal epithelium and below by the undifferentiated type of sinus epithelium which still occupies the upper part of the sinus (Pl. 3, fig. 17').


Associated with the increasing area of contact between the vagina and the sinus which gives rise to the hymen, the configuration of the sinus itself shows a considerable change from the stage represented by the 16% week foetus. The pars pelvina, as judged by the site of entry of the ducts of Bartholin’s glands (Text-fig. 4), is now very short, and the original system of longitudinal folds, though it can still be followed, has become modified by the change in shape of this part of the sinus.


A striking feature, which seems to be associated with the invagination of the upper part of the dorsal wall of the sinus by the lower end of the vagina, is the accentuation of the upper end of the lateral fold, now lying parallel with the posterior portion of the hymen and separated from it by an upward extension of the dorso-lateral sinus bay—the bay which, at a lower level (Text-fig. 4), receives the ducts of Bartho1in’s glands. The dorso-lateral bay extends cranially and ventrally on the lower aspect of the hymen as far as the hymeneal orifices, where it terminates as the lateral fold becomes continuous with the hymeneal fold. In addition, it gives off a cranial diverticulum which ascends for a short distance on the lateral aspect of the lower end of the Vagina (Pl. 3, figs. 15, 16), and presumably represents the cranial extremity of the dorso-lateral bay of the 16.5 week stage, maintaining its position despite the relative downgrowth of the lower end of the vagina.



Text-fig. 4. 140 mm. foetus. Median sagittal section through the vagina and the sinus, with the corresponding transverse sections (x 6§). The stippling indicates the vaginal epithelium, and the vestibule is shown only in outline. Because of the dilatation of the upper end of the sinus it is not practicable to indicate the folds of its wall in the median sagittal section. However, the dorsal margin of the lower part of the lateral fold is shown by the dotted line, and the small inset figure shows the outline (dotted line) of the upper end of the dorso-lateral sinus bay and its cranial diverticulum in relation to the margins of the vaginal and sinus epithelia (continuous lines) and to the hymeneal orifices (interrupted line). hy—hy’ indicates the level of the hymeneal orifices in relation to the median sagittal section. Other lettering as for Text-fig. 1. It will be seen that the change in the position of the lateral fold in this specimen, and to an even greater extent in the next (Text-fig. 5), differs from that described by Mijsberg (1924). The dorso-lateral bay is rotated relatively upwards and backwards with the downgrowth of the vagina into the sinus. According to Mijsberg, this bay is rotated upwards and forwards, an opinion for which the present material offers no evidence.


The hymeneal folds, bounding the outer margins of the paired hymeneal orifices, represent the dorsal margins of the urethro-vaginal folds of the earlier stages. In the same way they form the boundary between the differentiated and undifferentiated types of sinus epithelium, and it is by the enlargement of the area of differentiated epithelium - now the lower end of the vagina — and its downgrowth relative to the urogenital sinus that the hymen is formed. The mesodermal septum between the two hymeneal orifices seems to differ in origin from the remainder of the hymen, and probably results from the further development of a septum such as occurs in the 112 mm. foetus, splitting the root of the sinus upgrowth. By the enlargement and downgrowth of the lower end of the vagina the septum is projected forwards to divide the space between the dorsal margins of the urethro-vaginal folds — in other words, to split the hymeneal orifice. The mesodermal septum of the 140 mm. stage is therefore lined on both its ventral and dorsal aspects by vaginal epithelium.

180 mm Foetus

The enlargement and canalisation of the vagina now extends throughout its entire length, and the fornices are well established. An important change is the disappearance of the zone of stratified squamous Miillerian epithelium from the lower portion of the cervical canal, and the sinus epithelium of the vagina meets the columnar epithelium of the uterus just inside the external os. Here there is a very clear line of distinction between the two epithelia (Pl. 3, fig. 18). Both give a strongly positive PAS reaction, granular in the vaginal epithelium and diffuse in the columnar cells of the cervix, but in the latter this reaction is not affected by previous salivary digestion.


The vagina is lined by a very thick stratified squamous epithelium (Pl. 3, fig. 19), in which it is possible to distinguish four cellular zones. The basal zone is formed by three or four layers of small cubical cells, with relatively large nuclei and basophil cytoplasm. The next zone consists of seven or eight layers of much larger cells, with relatively much smaller nuclei and pale, acidophil cytoplasm. The deeper layers of this zone consist of polygonal cells, with deeply stained cell walls, but the three or four superficial layers are formed by very flattened cells, with much thicker cell walls. The third zone consists of about ten layers of large, clear-staining polygonal cells, less flattened and with thinner cell walls than the most superficial cells of the second zone. The nuclei are very small, and are absent from many of the cells. The innermost zone is formed by four or five layers of cells, similar to those of the third zone but more flattened. Many of the cells are without nuclei, and the nuclei which are present are very small and pyknotic.


Glycogen is extremely abundant in the vaginal epithelium in all but the basal zone of cells, as shown by staining with Best’s ammoniacal carmine and by the PAS technique. It is generally located as large granules, sometimes almost filling the cytoplasm of the cell, and is usually, but not always, restricted to the part of the cell on the proximal side of the nucleus. In addition, the cell walls of the three superficial zones show a positive PAS reaction after previous salivary digestion, similar to that demonstrated by Wislocki, Fawcett & Dempsey (1951) in the vaginal epithelium of the adult.


A further development from the 140 mm. stage is the lining of the under surface of the hymen and the adjacent portion of the vestibule by an epithelium similar to the vaginal epithelium, though rather thinner. Associated with the further relative downgrowth of the lower end of the vagina, and the resulting more horizontal position of the hymen (Text-fig. 5), the pars pelvina has almost disappeared. In fact, the shape of the sinus is so distorted from its original form that the distinction between pars pelvina and pars phallica now has little meaning.


By this stage the sinus extends further dorsally in relation to the under surface of the hymen, and the dorso-lateral sinus bays are very prominent, forming a dilatation of the vestibule immediately beneath the hymen (Text-figs. 5a, b). They extend further ventrally than in the 140 mm. foetus, reaching forwards around the sides of the anterior portion of the hymen. As before, they send short diverticula cranially, on either side of the lower end of the vagina. The hymenal orifice is unsplit.

200 mm Foetus

This specimen shows little further change, but the sagittal plane of section gives a very clear picture of the penetration of the lower end of the cervical canal by the vaginal epithelium, to a distance of about 3 mm. above the external os.

375 mm Foetus

The vaginal epithelium is now considerably thinner, but the lumen is filled with cell debris, suggesting that the decrease in thickness may be largely due to desquamation of the superficial cell layers. Only three cellular zones can be distinguished (Pl. 3, fig. 20). In the basal zone there are usually three layers of small cubical cells, with large nuclei and basophil cytoplasm. The intermediate zone is formed by four or five layers of much larger polygonal cells, with relatively smaller nuclei and deeply staining cell walls. Superficially there are two or three layers of large flattened cells with small pyknotic nuclei. The superficial and intermediate zones are not clearly distinct from each other, and both are rich in glycogen granules. It is possible that these two zones represent the second zone of the epithelium of the 180 mm. foetus, the third and fourth zones having been desquamated. Again the cell walls give a positive PAS reaction after salivary digestion.



Text-fig. 5. 180 mm. foetus. Median sagittal section through the lower end of the vagina and the vestibule, with the corresponding coronal sections ( x 4). The dotted line in the sagittal section shows the relative extent of the dorso-lateral bays. The coronal sections are shown with their cranial ends towards the top. a, urethra; v, vagina; h, hymeneal orifice; db, dorso-lateral sinus bay; cd, cranial diverticulum of dorso-lateral sinus bay.


The sinus shows the further progress of the developmental changes noticed at the 180 mm. stage. The dorso-lateral bays extend still further forwards, now reaching around the urethral orifice, and the dorsal extension of the sinus in relation to the under surface of the hymen is still more marked. The whole of the upper part of the sinus is lined by an epithelium similar to that of the vagina, and now of about the same thickness.

1 month Infant

Little change is noticed in this specimen, except in the character of the vaginal epithelium (Pl. 3, fig. 21). This is considerably thinner than in the later foetal stages and consists mainly of polygonal cells with relatively large nuclei, deeply staining cytoplasm and indistinct cell walls. Glycogen is no longer present, and the cell walls no longer give a positive PAS reaction.

Discussion

There can be little doubt that the epithelium of the human vagina is entirely derived from an upgrowth of sinus cells, as Vilas (1932), Kempermann (1935) and Meyer (1934-38) claimed, but the manner of formation of this upgrowth does not seem to be completely in accord with their findings. Vilas believed that the epithelium in the dorsal wall of the sinus proliferated in two different ways. An inner proliferation of pale-staining cells grew ventrally and medially in the internal layers of the dorsal sinus wall, meeting its fellow to form a crest which projected ventrally into the sinus lumen. An outer proliferation of darkly staining cells grew dorsally, displaced the Miillerian cells from the Miillerian tubercle and extended cranially as an epithelial plate, subsequently canalized to form the vagina. The views of Meyer and Kempermann were essentially similar.


It is interesting to compare this with Koff's account (1933) of the origin of the ‘sino-vaginal bulbs’, evaginations of the dorso-lateral aspect of the sinus on each side. Koff found that their epithelium was different from that of the rest of the sinus, consisting of well-marked basal and superficial zones, the basal cells darkly staining and the superficial cells pale-staining. The bulbs became larger and eventually fused with each other to form a solid cellular mass, which displaced the Miillerian tissue dorsally and cranially and eventually became canalized as the lower one-fifth of the vagina. The sino-vaginal bulbs seem to be the structures which have here been termed the dorso-lateral projections. In the same way they were joined by the lower ends of the Wolffian ducts, when these persisted, and carried the attachments of the duets with them as they extended cranially. Koff did not mention any proliferation of darkly staining cells from the intermediate portion of the dorsal wall of the sinus, such as occurs in the 65 mm., 68 mm. and 14-week foetuses of this present collection, and would presumably regard this proliferation as an early stage in the fusion of the sino-vaginal bulbs.


Up to a point, the findings of this present investigation combine both these views on the initial origin of the sinus contribution to the vagina, the sinus upgrowth taking origin from all three of the elements associated with the activity of the dorsal wall of the sinus, first noticed in the 65 mm. foetus. The junction of the persistent lower end of the left Wolffian duct with the sinus upgrowth in the 94 mm. specimen indicates that, at any rate in this foetus, the dorso-lateral projection must have participated in the formation of the upgrowth. On the other hand, in the 65 mm. foetus there seems no doubt as to the entity of the intermediate proliferation of darkly staining cells, and their contribution to the sinus upgrowth cannot be ignored. Only by the fusion of the three initial elements, by the 94 mm. stage, is the single sinus upgrowth produced. It is interesting that the formation of the sinus upgrowth in the human foetus bears such a close similarity to the initial origin of the lower vaginal segment in the sheep (Bulmer, 1956). There may be no great significance in the distinction between the dorso-lateral projections and the intermediate proliferation of darkly staining cells, all three representing a continuous cellular proliferation from this area of the sinus wall. There seems little doubt, however, of the identification of the dorso-lateral projections with Kofi"s sino-vaginal bulbs, and of the intermediate proliferation with the outer sinus proliferation of Vilas.


In many instances, it appears, the root of the sinus upgrowth is split at its origin from the dorsal wall of the sinus by the inclusion of a small mesodermal septum. Vilas pointed out that in his early foetuses, from the 38 mm. stage onwards, a small mass of mesoderm interrupted the contact between the Miillerian epithelium and the dorsal wall of the sinus in the midline, and this has been noticed here in the 28, 42 and 50 mm. foetuses. Vilas described the initial bilateral origin of the darkly staining sinus proliferation, the two origins then fusing to form a single sinus upgrowth. In the 65 mm. foetus, described here, there is no sign of such a bilateral origin, but in the 68 mm. foetus the proliferation is split by a small mesodermal septum. The inclusion of a mesodermal septum in the root of the sinus upgrowth is most probably a result of the persistence of such a septum at the Mfillerian tubercle, and this would suggest that the darkly staining proliferation only arises where the sinus is actually in contact with Miillerian cells. The persistence of such a septum, as in the 112 mm. foetus, and its development into a hymeneal septum, as in the 140 mm. foetus, must be fairly common, and occurred in many of the specimens examined by Meyer (1934-38). The persistence of a more extensive septum in the utero-vaginal canal would account, in a similar manner, for a congenital duplication of the vagina.


The further development of the sinus upgrowth, after the 94 mm. stage, is of some interest. Vilas found that as the Miillerian epithelium receded before the advancing plate of sinus epithelium the lower end of the utero-vaginal canal, including its whole ‘vaginal’ portion, became completely occluded by the proliferation of its lining cells. A solid vaginal plate was thereby formed, composed of Miillerian tissue above and sinus tissue below, but the sinus epithelium gradually extended further and further cranially until eventually the Miillerian epithelium was completely displaced from the vaginal plate. In the series of foetuses examined here the occlusion of the lower end of the utero-vaginal canal is not a prominent feature. It is first seen at the 65 mm. stage and persists until the Miillerian epithelium is completely excluded from the vagina, but it never involves more than a short segment. It is to be noted, however, that the Stratification of the epithelium of the utero-vaginal canal does extend, apparently by the 94 mm. stage, throughout the entire ‘vaginal’ portion of the canal.


Koff also described a ‘ primitive vaginal plate ’, formed in its lower portion by the solid epithelial mass of the sino-vaginal bulbs, and in its upper portion from the occlusion of the ‘vaginal’ portion of the utero-vaginal canal by the proliferation of its lining cells. In this solid vaginal plate Koff claimed that he was able to distinguish histologically between the sinus and Miillerian components, and only after the 142 mm. stage was this distinction no longer apparent. He assumed that the relative proportions of the two epithelia remained unchanged after this stage, the sinus epithelium being restricted to the lower one-fifth of the vagina.


Unfortunately, Koff showed no microphotograph of the epithelial distinction between the components of his primitive vaginal plate, but the criterion which he used for the identification of the sinus epithelium was its differentiation into external darkly staining and internal pale-staining zones. It has been noticed in the series of foetuses described here that after the 94 mm. stage the internal cells in the cranial part of the sinus upgrowth are much less pale-staining than they are further caudally. For instance, in the 16% week foetus the large, markedly pale-staining cells are restricted to the enlarged portion of the dorsal wall of the sinus and to the swellings at the caudal end of the sinus upgrowth. Indeed, Koff seems to have identified the two laterally placed swellings with the sino-vaginal bulbs themselves—a conclusion which is difficult to follow and for which there is no evidence in the material described here. The epithelium at the cranial end of the sinus upgrowth is of the same essential character as that further caudally. There is no evidence of any sharp histological distinction in the vaginal mass except the one which has been identified as the junction of the cranial end of the sinus upgrowth with the caudal end of the Miillerian tissue. Koff’s description offers no explanation for the very marked distinction between the two, occurring about half-way up the ‘vagina’ in the 16.5 week foetus.


The most likely explanation for the histological differences between the cranial and caudal ends of the sinus upgrowth is that the differentiation of its cells progresses from below upwards. Thus, the cells of the caudal end of the upgrowth in the 112 mm. and 16:} week foetuses, when the internal cells are larger, their nuclei smaller and the cell walls deeply stained with eosin, are similar to those occupying the whole of the lower half of the vagina in the 140 mm. foetus. The transversely elongated plate of the vagina appears to differentiate, at each particular stage, by first enlarging to form swellings. The epithelium correspondingly proliferates and the internal cells become large, with small nuclei and deeply stained cell walls. The swellings become still larger, and confluent with each other, the central cells then desquamating to form the vaginal lumen. The 140 mm. foetus shows later and later stages of this process as the sinus upgrowth is followed further and further caudally. The vaginal epithelium continues to proliferate, presumably under the influence of hormonal stimulation, and it is interesting to compare its structure in the two older foetuses with the adult vaginal epithelium as described by Papanicolou, Traut & Marchetti (1948), and more particularly, in view of the probable hormonal influences at work, with the vaginal epithelium of the pregnant woman, described by Smith & Brunner (1934).


As indicated above, many earlier workers have denied the participation of sinus epithelium in the formation of the vagina. Berry Hart (1896, 1901 and 1911) and Mijsberg (1924) described a contribution to the vagina from the ‘Wolflian bulbs’, proliferations of the epithelium of the lower ends of the Wolffian ducts. There seems no doubt that the Wolifian bulbs were the dorso-lateral projections, and there is no evidence that these latter arise from Wolflian epithelium. Their cells are unlike the cubical Wolffian cells which lie dorsal to them, and much more closely resemble those of the dorsal sinus wall. Berry Hart believed that the epithelium of the Wolffian bulbs extended throughout the entire vagina, while Mijsberg, in a sense less correctly, restricted the Wolffian contribution to a lower vaginal segment. His reasons for this were similar to those which influenced Koff to believe that the sino-vaginal bulbs formed only the lower end of the vagina.


Other authors have held to the view that the human vagina is entirely derived from the Miillerian utero-vaginal canal. Bloomfield & Frazer (1927) illustrated a section rather similar to the ones shown in P1. 1, figs. 4, 5 and 6, for the 65 mm. foetus, but their interpretation was very different, as they believed that the pale-staining cells in the dorsal sinus wall were the Miillerian cells breaking through into the sinus at the Miillerian tubercle. It is clear that the findings in the 65 mm. foetus make such a view untenable, and this misinterpretation presumably led Bloomfield & Frazer to think that the whole extent of the differentiated type of sinus epithelium was of Miillerian origin.


While the sinus origin of the vaginal epithelium appears to be established, one or two points of detail merit further consideration. From the earliest stage examined, represented by the 28 mm. foetus, the epithelium which lines the part of the sinus from which the sinus upgrowth later arises differs from that of the rest of the pars pelvina in consisting of two cellular zones——darkly staining cells deeply and pale-staining cells superficially. So far, it has been tacitly assumed that both these cell types are of sinus origin, but other workers have placed different interpretations upon them. Vilas (1932) believed that the darkly staining cells were of sinus origin, but was prepared to accept that the pale-staining cells were Wolffian, growing ventrally and medially in the dorsal wall of the sinus to form the ventrally projecting Wolflsche Kamm, identified by Kempermann (1931) and evident in the 65 mm. foetus of this present investigation. Kempermann (1935) also believed that the pale-staining cells were Wolffian in origin, but that they later completely disappeared. The pale-staining cells in the internal layers of the sinus upgrowth at a stage such as that represented by the 94 mm. foetus of this collection were not the Wolffian cells, but a new generation of cells derived from the sinus. Meyer (1934-38), however, believed that the pale-staining Wolffian cells did persist into later foetal life, identifying them with the large pale-staining cells such as occur at the root of the sinus upgrowth in the 112 mm. and 16.5 week foetuses.


This question does not seem possible of solution by ordinary histological methods. Nevertheless, the pale-staining cells in the dorsal wall of the sinus from the 28 mm. stage onwards bear no obvious similarity to the cubical cells which line the Wolffian ducts, and are distinct from the Wolffian cells which lie dorsal to them. It appears just as reasonable to suppose that the pale-staining cells are derivatives of the darkly staining basal cells, and that there is no incorporation of Wolffian cells in the dorsal wall of the sinus at this stage. No such ingrowth occurs in other mammals, and it seems unnecessary to postulate it in the human foetus. Nevertheless, it must be admitted that the differentiation of the sinus epithelium from which the sinus upgrowth arises is a remarkable feature, and it too has not been described in other mammals.


Also of some significance is the problem of the behaviour of the lower ends of the Wolifian ducts during the development of the vagina. Descriptions of the lower ends of the Wolffian ducts in female foetuses fall generally into two main categories. In the first are those which maintain that the Wolffian ducts continue to open into the sinus at their original site, immediately lateral to the position of the Miillerian tubercle. Thus, Meyer (1909) described the persistence of the lower ends of the Wolflian ducts in a large number of older foetuses and new-born children, running into the substance of the hymen and opening into the vestibule close beside the hymeneal orifice. On the other hand, many other workers (Tourneux & Legay, 1884; van Ackeren, 1889; Mijsberg, 1924; Koff, 1933) have described the cranial migration of the lower ends of the Wolffian ducts to join the lower end of the vagina itself, though the ducts degenerated very soon after and did not persist into late foetal life.


At first sight, the present investigation supports this latter view. In the 94 mm. foetus the lower end of the left Wolffian duct joins the sinus upgrowth, indicating that the dorso-lateral projection has carried the Wolffian remnant with it as it grew cranially, while in none of the older foetuses was there any trace of the lower ends of the Wolffian ducts. Nevertheless, this evidence is insufficient to suggest that the lower ends of the Wolffian ducts never maintain their openings into the sinus beside the original site of the Miillerian tubercle, particularly in view of the large number of such cases described by Meyer (1909). At that time Meyer regarded these Wolffian remnants as indicative of the entirely Miillerian origin of the vagina, but in his later publications (1934-38) pointed out that they were equally in accord with the account of vaginal development given by Vilas. The Wolffian ducts were not involved in the proliferation which Vilas believed to form the epithelial plate of the vagina, and were therefore left behind near the hymen. Nevertheless, the structures which Meyer now identified as persistent Wolffian remnants do not appear to occupy the same site as those which he had described earlier, but join the lower end of the vagina on the upper aspect of the hymen. In other words, they have been carried cranially for a short distance during the formation of the sinus upgrowth.


It may be that in some instances the lower ends of the Wolffian ducts are not carried cranially with the sinus upgrowth to such a great extent as they have been in the 94 mm. foetus, or indeed that they are not carried cranially at all. This may be because the dorso-lateral projections do not play such a large part in the formation of the sinus upgrowth in these cases, or because the manner of their growth is such as not to involve the lower ends of the Wolffian ducts. In other words, it is possible, as von Lippmann suggested (1939), though with rather a different purpose, that there is some variability in the behaviour of the lower ends of the Wolffian ducts during the early stages of vaginal development. This is supported by the fact that an ectopic ureter, presumably opening by a persistent Wolffian remnant, may join either the vagina or the vestibule (Kermauner, 1909). It is also possible that many of the structures which have been identified as persistent Wolffian remnants were, in fact, not so. In the 140 mm. foetus the dorso-lateral sinus bays end above by sending short diverticula upwards on either side of the lower end of the vagina, lined by the undifferentiated type of sinus epithelium. In the 180 mm. foetus these diverticula are still lined by the undifferentiated epithelium, though the dorso-lateral bays themselves are occupied by an epithelium very similar to that of the vagina. The diverticula are presumably associated with the relative downgrowth of the lower end of the vagina, as has already been pointed out. They are, however, very similar to the ‘Wolffian remnant’ described by Bloomfield & Frazer (1927), in a 170 mm. foetus of their collection, but their lining epithelium leaves no doubt of their origin (Pl. 3, fig. 16).


An interesting viewpoint on the development of the vagina was suggested by Zuckerman (1940), who believed that any epithelium of the adult genital tract which responded to oestrogenic stimulation by a stratified squamous proliferation—a ‘squamous response ’—was a derivative of the sinus epithelium of the foetus. The conclusion of this present investigation, that the entire vaginal epithelium is derived from the sinus upgrowth, might appear to support Zuckerman’s hypothesis. There is, however, a considerable body of embryological evidence which indicates that in many other mammalian forms the upper vaginal segment, though it is lined by a stratified squamous epithelium and gives a squamous response to oestrogenic stimulation, is a Miillerian derivative. Thus, it seems likely that when the Miillerian epithelium does persist in the vagina it tends to be of stratified squamous form and its response to oestrogenic stimulation squamous in type. Of some interest in this respect is the lining of the ‘ vaginal ’ portion of the utero-vaginal canal in the human foetus by a stratified squamous epithelium of Miillerian origin, and the disappearance of this epithelium after the 140 mm. stage, when it is displaced into the cervical canal. In the absence of any firm knowledge of the hormonal conditions in female human foetuses, we do not know how this stratified Miillerian epithelium responds to oestrogenic stimulation. Probably, however, there is some controlling factor, producing its effect in foetal life in the human subject and throughout life in many other mammals, which stimulates Miillerian cells in the vagina, but not in the uterus, to form a stratified squamous epithelium.


One of the most interesting problems is that of the extent to which the development of the human vagina is influenced by hormonal factors. It is a reasonable supposition that the enormous activity of the vaginal epithelium in the older foetuses is a result of stimulation by maternal oestrogens, as Fraenkel & Papanicolou (1938) suggested. The gross differences between the vaginal epithelium in these foetuses and that of the 1-month old infant imply that this oestrogenic stimulation must extend over a considerable period of foetal life—at any rate from the 112 mm. stage onwards. The question of the hormonal control of genital development has introduced a new field of experimental embryology, in which a very large amount of work has already been carried out (for bibliography see J 0st, 1948), and it raises many interesting problems concerning the development of the human vagina. It may be that the enormous enlargement of the lower end of the vaginal mass at the 140 mm. stage, associated with the formation of the hymen, is a result of hormonal stimulation to which only the differentiated type of sinus epithelium is sensitive. At an earlier stage, the extension of the sinus upgrowth itself may be due to a similar selective response of the differentiated epithelium. Some of the marked differences between vaginal development in man and in other mammals may result from differences in the degree of hormonal stimulation at various critical periods of foetal life, rather than from inherent differences in the structures which go to form the vagina. On the other hand, the histological differentiation of the epithelium of the sinus upgrowth in the human foetus may be associated with an increased sensitivity to hormonal stimulation, compared with other mammalian forms. While such suggestions can be only tentative, it is, nevertheless, very likely that the endocrinology of vaginal development holds the key to many of these outstanding problems.

Summary

  1. The development of the human vagina has been studied from a series of female foetuses ranging from 28 to 375 mm. crown-rump length, and from a 1-month old infant.
  2. An upgrowth arises from an area of ‘differentiated’ epithelium in the dorsal Wall of the sinus, in a manner which might be said to combine the descriptions of Vilas (1932) and Koff (1933).
  3. The sinus upgrowth extends throughout the entire region of the vagina by the 140 mm. stage, and forms the Whole of its epithelial lining. The changes in the vaginal epithelium of older foetuses are also described.
  4. The findings are discussed in relation to the question of an early ingrowth of Wolffian epithelium into the dorsal wall of the sinus, the problem of the behaviour of the lower ends of the Wolffian ducts in female foetuses, and recent opinions on the significance of the sex hormones in genital development.


My thanks are due to Prof. J. D. Boyd, for the loan of most of the material which I was able to study. I am also indebted to Messrs J. F. Crane and A. Cain for the microphotographs, and to Mr W. Cruickshank for his assistance with the diagrams.

References

ACKEREN, F. VAN (1889). Beitrage zur Entwicklungsgeschichte der weiblichen Sexualorgane des Menschen. Z. wiss. Zool. 48, 1-46.

BANKS, W. M. (1864). On the Wolfiian Bodies of the Foetus. Edinburgh.

BLOOMFIELD, A. & FRAZER, J. E. (1927). The development of the lower end of the vagina. J. Anat., Lond., 62, 9-32.

BOLK, L. (1907). Beitrage zur Affenanatomie VI. Zur Entwicklung und vergleichenden Anatomic des Tractus urethro-vaginalis der Primaten. Z. Morph. Anthr. 10, 250-316.

BULMER, D. (1955). The Development of the Vagina. Thesis for the degree of M.D., University of Cambridge.

BULMER, D. (1956). The early stages of vaginal development in the sheep. J. Anat., Lond., 90, 123-134.

FELIX W. (1912). The development of the urogenital organs. In Keibel and Mall, Manual of Human Embryology, Vol. II, p. 752. Philadelphia and London.

FRAENKEL, L. & PAPANICOLOU, G. N. (1938). Growth, desquamation and involution of the vaginal epithelium of human foetuses and children, with a consideration of the related hormonal factors. Amer. J. Anat. 62, 427-451.

GOMORI, G. (1952). Microscopic Histochemistry. University of Chicago Press.

HART, D. B. (1896). Preliminary note on the development of the clitoris, vagina and hymen. J. Anat., Lond., 31, 18-28.

HART, D. B. (1901). Morphology of the human urogenital tract. J. Anat., Lond., 35, 330-375.

HART, D. B. (1911). Adenoma vaginae diffusum (adenomatosis vaginae), with a critical discussion of present views of vaginal and hymeneal development. ‘Edinb. med. J. 6, 577-590.

HUNTER, R. H. (1930). Observations on the development of the human female genital tract. Contr. Embryol. Carneg. Inst. 22, 91-108.

J os'r, A. (1948). Le controle hormonal de la différenciation du sexe. Biol. Rev. 23, 201-236.

KEMPERMANN, C. T. (1931). Beitrag zur Frage der Genese der menschlichen vagina. Gegenbaurs Jb. 66, 485-531. A 508 D. Bulmer

KEMPERMANN, C. T. (1935). Beitrage zur Entwicklung des Genitaltraktus der Sanger. III. Das Schicksal der kaudalen Enden der Wolffsche Gange beim Weibe und ihre Bedeutung fiir die Genese der Vagina. Gegenbaurs Jb. 75, 151-179.

KERMAUNER, F. (1909). Die Missbildungen der weiblichen Geschlechts-organe. In Schwalbe, Die Morphologie der Missbildungen des Menschen und der Tiere, Jena. T. III, p. 253.

Koff A. Development of the vagina in the human fetus. (1933) Contrib. Embryol., Carnegie Inst. Wash. Publ. 443, 24: 59-60.

LIPPMANN, R. VON (1939). Beitrag zur Entwicklungsgeschichte der menschlichen Vagina und des Hymen. Z. Anat. EntwGesch. 110, 264-300.

MEYER, R. (1909). Zur Kentniss des Gartnerschen (oder Wolffschen) Ganges besonders in der Vagina und dem Hymen des Menschen. Arch. mikr. Anat. 73, 751-792.

MEYER, R. (1934-1938). Zur Frage der Entwicklung der menschlichen Vagina. I. Arch. Gynaek. 158, 639-738; II, Arch. Gynaelc. 163, 205-308; III, Arch. Gynaek. 164, 207-357; IV, Arch. Gynaelc. 165, 504-590; V, Arch. Gynaelc. 167, 306-338.

MIJSBERG, W. A. (1924). Uber die Entwicklung der Vagina, des Hymen und des Sinus urogenitalis beim Menschen. Z. Anat. EntwGesch. 74, 684-760.

MULLER, J . (1830). Bildungsgeschichte der Genitalien. Dusseldorf: Arnz.

PAPANICOLOU, G. N., TRAUT, H. F. & MARCHETTI, A. A. (1948). The Epithelia of Woman’s Reproductive Organs. Commonwealth Fund, New York.

POLITZER, G. (1952). Das Schicksal des Sinus urogenitalis beim Weibe. Z. mikr-anat. Forsch. 59, 6-28.

POLITZER, G. (1955). Zur normalen und abnormen Entwicklung der menschlichen Scheide. Anat. Am. 102, 271-278.

RATHKE, H. (1832). Abhandlungen zur Bz'ldungs- und Entwrlclclungsgeschichte des Menschen und der Thiere. Leipzig. 1

RETTERER, E. (1891). Sur l’origine du Vagin de la femme. C'.R. Soc. Biol., Paris, Ser. 9, 3, 291-293.

SMITH, B. G. & BRUNNER, E. K. (1934). The structure of the human vaginal mucosa in relation to the menstrual cycle and to pregnancy. Amer. J . Anat. 54, 27-85.

SPULER, A. (1930). Entwiclclungsgeschichte des weiblichen Genitalapparates. In Veit-Stoeckel, Handbuch der Gyniikologie, 3rd ed., Band I, p. 470 (quoted by Vilas). Wiesbaden.

TOURNEUX, F. & LEGAY, C. (1884). Mémoire sur le développement de l’uterus et du vagin. J . Anat. Paris, 20, 330-386.

VALENTIN, G. G. (1835). Handbuch der Entwicklungsgeschichte des Menschen. Berlin.

VILAS, E. (1932). Uber die Entwicklung der menschlichen Scheide. Z. Anat. EntwG'esch. 98, 263-292.

W1sLocK1, G. B., FAWCETT, D. W. & DEMPSEY, E. W. (1951). Staining of stratified squamous epithelium of mucous membranes of Man and Monkey by the periodic acid-Schiff method. Anat. Rec. 110, 359-376.

ZUCKERMAN, S. (1940). The histogenesis of tissues sensitive to oestrogens. Biol. Rev. 15, 231-271.

Explanation Of Plates

Plate 1

Bulmer1957 plate01.jpg

Fig. 1. 28 mm embryo. Transverse section through the openings of the Wolffian ducts into the urogenital sinus. The sinus epithelium consists of basal deeply staining and superficial pale-staining cells, and the pale-staining cells extend for a short distance into the lower ends of the Wolffian ducts. The Miillerian ducts are in close relation with the Wolflian ducts, but a small mass of mesoderm separates them from the sinus. ( x 215.)

Fig. 2. 48 mm foetus. Sagittal section through the opening of the right Wolfiian duct. The differentiation of the sinus epithelium in this region can be seen, and the extension of the pale-staining cells into the lower end of the Wolffian duct. (x 215.)

Fig. 3. 65 mm foetus. Transverse section through the genital cord. The Wolffian ducts are very small structures, on either side of the utero-vaginal canal. ( x 215.)

Fig. 4. 65 mm foetus. Transverse section through the junction of Mullerian and sinus epithelia. A mass of darkly staining cells (d), arising from the dorsal wall of the sinus, separates the caudal end of the Mullerian epithelium (m) from the sinus lumen. On the right side the section passes below the bulk of the dorso-lateral projection, and the Wolffian duct is large. On the left the Wolffian duct is a small structure, applied to the dorsal aspect of the dorso-lateral projection (dp). (x 215.)


Fig. 5. 65 mm foetus. Transverse section 16 p. caudal to Fig. 4. The Mullerian epithelium now forms a smaller mass dorsally, and a few of the darkly staining sinus cells separate it from the pale-staining sinus epithelium ventrally. ( x 215.)

Fig. 6. 65 mm foetus. Transverse section 8 ,u caudal to Fig. 5. ( x 215.)


Plate 2

Fig. 7. 94 mm. foetus. Coronal section through the cranial and dorsal enlargement of the sinus which forms the root of the sinus upgrowth. The epithelial differentiation is very weH marked. ( x 84.)

Fig. 8. 94 mm. foetus. Coronal section through the sinus upgrowth, 90 ,u. dorsal to Fig. 7. The small darkly staining cells in the centre of the section (m) represent the caudal tip of the Mullerian epithelium. A thin layer of darkly staining cells forms the outer layer of the sinus upgrowth, and there is a small mass of these cells on the right (to the left of the photograph). 90 /1. further dorsally, a similar small mass, on the other side, is joined by the persistent lower end of the left Wolffian duct. ( x 215.)

Fig. 9. 112 mm. foetus. Transverse section through the dorsal part of the sinus, showing the two roots of the sinus upgrowth separated from each other by the mesodermal septum (ms). The pale-staining internal cells of the sinus are very prominent. ( x 215.)

Fig. 10. 112 mm. foetus. Transverse section through the vaginal mass, 288 /1. cranial to Fig. 9. The sinus upgrowth forms two lateral wings, while the central portion (m) is formed by the paler-staining polygonal cells of the caudal end of the Miillerian tissue. ( x 215.)

Fig. 11. 16.5 week foetus. Transverse section through the junction of the Miillerian epithelium of the utero-vaginal canal (m) with the cranial wing of the sinus upgrowth on the left side. ( x 215.)

Fig. 12. 16.5 week foetus. Transverse section through the sinus showing the junction of its dorsal wall with the caudal end of the sinus upgrowth. The central enlargement of the upgrowth is immediately dorsal to the sinus lumen, and a further enlargement projects dorsally from it. The large clear-staining internal cells are prominent in the central enlargement. In the dorsal enlargement the cytoplasm and cell boundaries of the internal cells are markedly eosinophilic. ( x 84.)

Fig. 13. 140 mm. foetus. Transverse section through the left side of the cervical canal, showing the junction between the stratified Miillerian epithelium (m) and the cranial tip of the sinus upgrowth. ( x 160.)

Plate 3

Fig. 14. 140 mm. foetus. Transverse section through the left vaginal enlargement, just below the middle of the cranio-caudal extent of the vagina. The internal cells are large, their nuclei relatively small and the cell-boundaries markedly eosinophilic. ( x 215.)

Fig. 15. 140 mm. foetus. Transverse section through the urogenital sinus and the lower end of the vagina, at the level of the paired hymeneal orifices. On each side of the ventro-lateral aspect of the vagina is the small cranial extremity of the dorso-lateral sinus bay (db). ( x 30.)

Fig. 16. 140 mm. foetus. Transverse section through the wall of the dorso-lateral sinus bay, showing its lining of undifferentiated sinus epithelium. ( X 450.)

Fig. 17. 140 mm. foetus. Transverse section through the lower portion of the hymen, showing the vaginal epithelium above, separated by the hymeneal connective tissue from the undifferentiated sinus epithelium below. ( x 450.)

Fig. 18. 180 mm. foetus. Transverse section through the junction of the vaginal epithelium with the colunmar epithelium of the cervix. ( x 120.)

Fig. 19. 180 mm. foetus. Section through the vaginal epithelium. ( x 280.)

Fig. 20. 375 mm. foetus. Section of the vaginal epithelium overlying a mesodermal papilla. ( x 280.)

Fig. 21. Vaginal epithelium in the 1-month old infant. The epithelium is not of uniform thickness, and this photograph is taken from an area where it is rather thicker than usual, in order to give a better impression of its histological structure. (x 320.)



Cite this page: Hill, M.A. (2021, January 21) Embryology Paper - The development of the human vagina. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Paper_-_The_development_of_the_human_vagina

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