Book - Human Embryology (1945) 4
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Hamilton WJ. Boyd JD. and Mossman HW. Human Embryology. (1945) Cambridge: Heffers.
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Chapter IV Fertilization, Cleavage and Formation of the Germ Layers
There are great difTerences m the size of the mature unfertilized egg m difTcrent \ertcbrates (see Chapter WI) With the exception of monotrcmcs the eggs of mammals are small and contain httle deutoplasm oik) , i c the> ate miolecithal In the cuthenan mammals the diameter of the shed egg lies between 8o/i and 150^1 The eggs however often show distinctive characteristics m the appearance of the cytoplasm or vitellus In some mammals the parts of the vitellus are arranged m such a way that the ovaim exhibits distinct polaritv one half is rich m cvtoplasm and poor in deutoplasm the other is nch in deutoplasm and poor in cytoplasm (Fig 25) The polar bodies arc extruded at the cytoplasmic pole and the retained nuclear material the female pronucUus, lies nearer to tins pole
Fertilization is the act of fusion of the male and female gametes to form the zygote In mammals as m birds and reptiles the union of the male and female sex cells takes place wiihm the bodv of the female In these vertebrates the semen is deposited m the female genital tract bv a special intromittent organ the penis the act accompanying the deposition of the semen is called coitus or copulation The actual deposition of the seminal fluid in the vagina IS tnsmwalion
G '>3 — \ teciion of a ferret zygote with eccentrically placed pronuctei at approx 47 hours after insemination The polarity u evident by the presence of a cytty plasmic crescent which is more darkly stained.
Unfertilized Human Ova
Shortly after ovulation the human ovum surrounded by the corona radiata passes into the uterine tube (Hamilton 1944 Figs 26 and 27) Soon however the corona radiata cells degenente and separate from the zona pellucida Allen et al (1930) Lewis (1931) and Pmeus and Saunders (1937) have recovered living unfertilized human ova at this stage In the living ovAim the zona pellucida appears as a translucent and apparently structureless membrane
The diameter of the ovaim including the zona pellucida varies in the human ova which have been described The Lewis ovaim had a mean diameter of 148^. in other unfertilized ova described the diameter varied from 115/1-134/1 In the Lewis ovum the vitellus completely filled the zonal cavity and had a mean diameter of 136/t m some ova the vitellus does not fill the zonal cavity so that a periuttlline space is present The vitellus is surrounded by a structureless vitelline membrane In the living state the vilcUus is slightly yellowish in colour with a clearer outer zone and a darker central part On account of the refractilc nature of the vitellus it is impossible in the living human egg to sec the nuclear apparatus
PROCESSES PRELIMINARY TO FERTILIZATION
In the act of fertilization the male and female gametes {i e sperm and ovum) fuse together and form the zygote In man as m other mammals fertilization normally occurs m the ampulla of the uterine tube Before describing the process of fertilization the transport of the spermatozoa and ovum must be discussed.
Fig 26 — Photomicrograph of a living human ovum surrounded by the corona radiata recovered from the uterine tube X 480 (Original ) (Reproduced by the courtesy of the j of Anat )
Seminal Fluid.
The seminal fluid, or semen, is a complex mixture derived mainly from the testes, the seminal vesicles and the prostate gland The bulbo-urethral gland and the glands of the urethra provide a small amount of pie-ejaculatoiy lubricating fluid The fluid in man, m a normal ejaculation, amounts to about 3 c c , and contains 200-300 million spermatozoa, In the semmifei ous tubules the sperms are non-motile, as they are passed along the vas deferens by the ciliaiy and muscular activity of this duct they become mature and, after ejaculation, motile, the tail performing an undulating movement which piopels the sperm foiuard The secretions derived from the accessory glands help to activate the sperms and at the same time provide a carrying medium for them Examination of the semen has become important in the study of fertility The numbei, motility and abnoimalities in Size and shape of the sperms are all of importance in assessing the possible responsibility of the male partner in sterility (For literature and discussion see Weisman, 1941, and Joel, 1942 )
Transport and Viability of the Sperms. In mammals, It IS kno\vn that sperms pass very rapidly into the uterus and fiom it into the uterine tubes (Hartman and Ball, 1930, F^rker, I93U Florey and Walton, 193 ^’ Chang and Pincus, 195O They are rarely found, hoive\ er, in large numbei s in the uterine tubes It IS partly by their own activity, the undulatory movements of their tails, that the sperms pass into the cervical canal and the cavity of the uterus They are able to swim against the current produced by the ciliary action of the utenne
CLEAV\GE \ND FOR\t\TION OF THE GERM UX^ERS
rpithclmm Talmc\ (1C117) and Scgm ind Vineux (1933) that the uterus ma% ha%e a sucUn^ action dunng the orgasm u hich rm> dnxs the sperms into the ccrMca! canal omm howcser uho do not experience an orgasm during coitus seem to be as fertile as women who react normalK \ficr coitus in the rat Rossman (tq37J has shown that sperms arc aspirated mtn the uterus and passed rapidK along it 1 j\ its muscular contraction
Fate of the Sperms in the Female Genital Tract There is reason to behcNc that human sperms like those of moit mammah, ha\e a short Ide in the female genitil tract Most of the sperms are dead withm a peiwsd of four da\-s fCaia 1936) and m most mammals
ihes base lost their fertilizing power e\cn earlier Hammond 1923! * There is a correlation between sperm acti\it\ and abiht\ to fertilize the Q\aim but the greater the motility the more rapid will be the loss of fertilizing power Tlic sertetions found in the vacma dcstcos the fertihrint, power of the sperm after a short period Uithin narrow limits the more acid tiie secretion the less motile arc the sperms alkalmils on the other hand increases their motihts hence the shghth alkaline
uicnne secretions are fwourable for sperm transport
Transport of the Ovum through the Uterine Tube The o\um when extnided from the osars soon enters the ^nfundthulum or funnel of the uterine tube apparently vsashed into It fay currents m the peritoneal and follicular fluid created In the actniu of the cilia of the infundi bulum and its fringe of fimfanac The latter are applied to the osarian surface ^\^cstman 19371 The tulie IS lined with cihatnl epithelium scattered throughout which arc some non ciliated cells (Corner 1932J At the time of osailation the musculature of the tube is contracting rhythmically The o\um is passed along the tube fas the muscular contractions and bs the acti\ ity of the cilia There
• The length ol life of ihe sperms afier rjaculaiion can b» increased by suuabfe condiUons of storai; (llammcnd 1941 1 This IS of considerable imporiancc »n ihr rrenomin of sicxkbre dint; It has been st osw m the bone lhai sperms ha\ a longer fertilizing life (up 10 6 daysi than in most mammais Insomebais apparenOv (Hartman Uimssti 19441 th sperms can surMsemihcutmis during the winter and are capable of fertilizing an enum in the folios in? spring Sod rwall and Blandau (*9411 have shown that the fertilizing capacitt of sperms araiiciallt Wi mmattd in todents is e\cn less than is usually thought The fig ires they gv\e are 6 hours (moiisci to 30 boui irabbit) Chang (19 ,i> has shown ihai the fertibzinsr ptw er of sperms is increased by a sojourn in the uterus
Fro "8 — Sections of cleas age stages of the egg ofrhegoldenhamscer Cnctlutaumius x 640 \ CentralU placed pronuclei R First cleat age spindle C a celled stage D Second cleavage spindles at right angles to each other iReproduced from Boyd and llamil tor in Physiology of Reproduction b\ kind permission of Messrs Longmans Green
IS no definite knowledge of the time taken by the human ovum to traverse the tube, in lower mammals it is usually three to four days and presumably it is the same in the human subject the time required appears to be independent of the length of gestation and of the size, length and calibre of the tube
It IS now established, m the human subject, that an ovum from one ovary can pass to the opposite uterine tube, when the tube of the same side has been removed (transperitoneal migration) Whether the ovum actually migrates across the peritoneal cavity, or the tube reaches across to embrace the ovary at ovulation, has not been settled. For discussion of migration of the ovum in mammals see Boyd et al (1944).
Viability of the Ovum. It is known, from animal experiments, that the mammalian ovum IS only capable of being fertilized for a short time after ovulation. Hammond (1941) has shown that if fertilization does not take place within a limited period after shedding (rabbit, 12 hours, guinea-pig, q 6 hours; ferret, 30 hours) the ovum undergoes degenerative changes. If fertilization occurs, the ovum, now called the zygote,'*' undeigoes cleavage during its passage along the uterine tube (Fig 32)
Fertility. Fertility depends upon
Fig 29 — Photomicrograph of the 2-cclled stage of the human zygote x 500 (Reproduced by the courtesy of Drs Hertig and Rock )
the co-oidination of many different processes and upon the normal functioning of both male and female reproductive organs Whether fertilization in the normal mature female results from insemination depends on (i) the time interval between insemination and ovulation, (2) the length of time that the ovum remains fertilizable, (3) the number of spermatozoa reaching the uterine tube, (4) the time taken by the spermatozoa to reach the ovum in the tube, (5) the length of time during Avhich the spermatozoa retain their fertilizing power, (6) other factors in the semen which influence fertilization One of these appears to be the presence of a sufficient quantity of the enzyme, hyaluronidase (Rowlands, i 944 )'
Fertilization
In an earlier section, fertilization was described as the fusion of the male and female gametes. In the majority of mammals so far studied m this respect the oocyte, surrounded by the corona radiata, is shed from the ovary with the first polar body extruded and the second maturation spindle formed. It is at this stage of development that it is penetrated by the fertilizing In all but one or two of the relatively small number of mammalian species investigate , an probably in the human subject (Hamilton, 1944), the spermatozoa meet the ovum in the cepha ic portion of the uterine tube Only one sperm of the many deposited in the female genital trac IS required to fertilize the ovum Additional sperms may be found attached to the zona pelluci a or may even be found in the perivitellme space (Pincus, 1936), but they take no part in future development.
The sperm can enter the ovum at any point on its circumference In many mammals t e entire sperm is known to pass into the cytoplasm of the ovum After the entry of the the second polar body is extruded and the chromosomes which remain in the ovum themselves into a vesicular nucleus, the female pronucleus (Figs 25 and 28A) The vi e
Theoretically, the term ovum should not be used after the commencement of p" human embryology, however, the term is loosely applied up to the late blastoeyst and early pre-somite stag
shrinks so that a distinct pernitellmc space is present The head of the sperm undergoes changes after it enters the ovum, it swells and becomes transformed into the male pronucleus (Fig 28A) A human pronuclear stage has been described b> one of us (Hamilton 1949) The middle piece and tail persist for a short time later the\ are no longer \isib!e apparently becoming absorbed b> the cytoplasm of the osaim
After the head of the sperm has become detached from the middle piece and tail it probably rotates through 180 as it passes towards the female pronucleus which now approaches the centre of the ovum The two pronuclei soon meet in approximately the centre of the o\'um (Fig a8A) A centrosomc, which is possibly derived from the proximal centriole of the sperm, now becomes distinct It dmdes into two parts each of which is attached to a pole of the spindle which now makes its appearance (Fig 28B) At the same time each pronucicus resolves Itself into Its chromosomes and the nuclear membranes disappear The chromo somes of both pronuclei arrange themselves on the spindle and each splits longitudinally the resulting halves passing towards the cenlrosomes Opposite the equator of the spindle a circumferential furrow develops on the surface of the zygote it deepens until the cytoplasm is divided into two giving nse to a two cell st ige of the embryo or ovum (Fig 28B and C) Each of the daughter cells contains an equal number of paternal and maternal chromosomes (Chapter II) The polar bodies persist for a variable period of time m the penvitelline space (Lewis and Hartman 1933, and Hamilton 1934) but they eventually degenerate and disappear
The main results of fertilization are the restoration of the diploid number of chromosomes the determination of the sex of the zygote and the initiation of cleavage It must be realized, however that while with the exception of the sex chromosomes the egg and sperm are equivalent m chromosome content there is an immense disparity in the amount of cytoplasm contnbuted to the zygote from the two sources It is because of this that the influence of the egg on dev clopment is greater than that of the sperm The cy toplasm of the oocyte is organized before fertilization and in many species shows striking polarity Hence during cleav age cells which differ qualitatively are produced and these differences are of cytoplasmic rather than of immediate chromosomal origin
Parthenogenesis In many invertebrates and lower vertebrates it is possible to stimulate the oocyte to undergo cleavage in the absence of spermatozoa (Loeb 1913 and Morgan 1927) This artificia] parthenogenesis (to be carefully distinguished from artificial insemination) may result m the development of mature partheno^enetic adults Parthenogenesis of course occurs normally in many invertebrates In mammals there is some evidence that the ovarian egg may attempt to undergo cleavage but this never results in organized development (Pincus 1936) though it mav be
Fic- jO —I holographs of living eggs of the macaque monLcs stage &— three cel! stage C— four cell stage D — five cell stage stage F —eight cell stage ( \fter Lev is and Hartman 1933 ) of tf e Carnegie Institution of Washington y c *00
A — two-cell E — SIX cell Bv courtes)
involved in the pathology of teratomata Pincus (1939) has succeeded in stimulating development artificially in ripe unfertilized rabbit ova which, when transplanted to the uteri of uninseminated females, developed into parthenogenctic individuals
Cleavage
Cleavage consists of a rapid succession of mitotic divisions resulting in the production of a progressively larger number of increasingly smaller cells, called blastomeres. Although the cells increase m number during cleavage this mechanism is not a growth process m the usual sense of this term as there is no increase in protoplasmic volume during its occurrence. In fact the protoplasm decreases in amount as the result of metabolic activity. The principal effects of cleavage are three in number Firstly, there is a partitioning of the protoplasm of the zygote amongst the blastomeres. Secondly, an increased mobility is conferred on the original protoplasmic mass with consequent facilitation of the morphogenetic movements and rearrangements of later development. Finally, as the fertilized ovum, even m mammals, is much larger than the average adult cell size, cleavage results progressively in an approximation in size of the developing cells to that characteristic of the definitive cells of the organism. In this respect cleavage can be considered as a mechanism for the automatic re-establishment of the cell size normal foi the species concerned
Cleavage is classified in several different ways (see Chapter XVI) In descriptive embryology it is usual to classify the process according to the pattern of the divisions This pattern is largely dependent on the amount and distribution of the deutoplasm stored in the ovum. As there is only a small amount of such material in the true mammalian ovum there is little impedance to cell division so that cleavage, in eutheria, involves the whole ovum and results in the production of a numbei of equivalently-sized cells. Such cleavage is total (01 holoblastic) and equal.
Only a few human cleavage stages are known Hertig and Rock (1950) have described a two-cell stage recovered from the uterine tube (Fig 29) In addition they have described stages (probably abnormal) of eight, nine and twelve blastomeres which resulted from in vitro fertilization of human ovarian ova (Rock and Hertig, ^94^) It IS necessary, therefore, to refer to other mammalian material for a description of the details of cleavage Many accurate and detailed descriptions of the cleavage of the ova 0 mammals, m both living and fixed material, are now available The present account is base mainly on the monkey ovum, as described by Lewis and Hartman ( 1933 ) the species Macacus rhesus since this species is more closely related to the human than any other form m which cleavage has been studied The account, however, has been supplemented, where necessary, by references to other types
The first cleavage division has not been observed in the monkey, but it is probably menihona as it is in most mammalian eggs A two-cell stage was recovered from a monkey 292 after ovulation It was cultivated in vitro and remained in the two-cell stage for 7 hours cells were oval and lay parallel to each other (Fig 30A) They were unequal in size as is olten the case in two-cell stages of mammals. The cytoplasm was uniformly granular except in the neighbourhood of the nucleus, where it appeared as a clear area, and at each side of the nucleus the cenlrosphere and yolk material could be seen The nucleus of each cell became ^nvisi about hours before the next cleavage; this corresponds to the onset of the prophase. -1
Fig 31 — A photograph of the living morula of the macaque monkey (After Lewis and Hartman, 1933 ) By courtesy of the Carnegie Institution of Washington X c 300
distinct polarity described in man> mammalian two cell stages was not recorded The division at the two cell stage v^as dichotomous but the cells did not divide s>nchTonousl> At this stage as at subsequent stages the larger cell divided 6rst. so that a three cell stage was found (Fig 30E) The smaller cell of the two cell stage then divided and the cleavage planes of the two cell stage vs ere approximate!) at right angles to each other so that the cells of ihe/our cell stage, consisting of tuo larger and two smaller cell, la) crosswise (Fig 30C) the larger cells of this four cell stage divided before the smaller cells so that stage:, office sve seien and eight cells viere found (Fig 30H, E and ?) The axes of the spvndles which divided the cells were again probabl) at right anjes to each other m each pair of cells as in most mammals but this was not observed for the monke) The cells at the eight cell stage were so arrai^ed that the four celb derived from the larger cell
Fic 3 — \ sehcmaiic representation of the de\elopm»nt of the ovanan follicle its growth maturation and rupture Successive stages m the passage of ihe ovum into the tube and its fertilization subse quenV development and imptaniation are depicted (Based on DicVinson ) (i) Unsegmented Doe>le
at the ■’nd maturalion spindle (3) Fertilization (3) Eccentrically placed pronuclei and polar bodies (4) 1st sp ndle of division (5) Two-cell stage (6) Four cell stage (7) Eight cell stage (81 Xforula (9) and (10) Free blastocyst m uterine cavitv (11) Earl) phase of implantation (approvimately at the seventh day after ovTilation)
of the two cell stage were at one pole and the four cells derived from the smaller cell were at the other pole The cells of the eight cell stage in mammals continue to divide at different rates so that stages with nine ten etc to suteen cells are found At about the sixteen cell stage (Fig 31) the ovum of the monkev reaches the uterus and is known as the morula It consists of a group of
centrall) placed cells {inner cell mass) completely surrounded b) a peripheral la)er of cells (the future trophoblast) A morula w as recov ered from the uterus of the monkey 96 hours after ovoilation In the morula all the cells were of similar appearance, but subsequent development shows that the process of dcav age has brought about segregation of embry onic material so that it possesses a mosaic pattern despite its apparent uniformity of structure This segregation permits future differentiation as a result of potentialities whKh are inherent m the cells but these potentialities may be modified by environmental conditions (Chapter Vlll)
Le%vis and Hartman (1933) give a provisional estimate of the duration of the different cleavage stages of the eggs of Macacus rhesus as follows ; —
1 - cell stage . from ovulation to 24 hours after.
2- cell stage . „ 24 hours to 36 hours
3- 4-cell stage „ 36 „
5-8-cell stage . . ,,48 „
9- 1 6-cell stage . „ 72 „
There are no data of the precise time taken by human ova to reach the uterus, nor is the interval between ovulation and implantation known. A scheme showing the presumed developmental stages during the descent of the human ovum is given m Fig. 32. In the macaque monkey the blastocyst begins to implant m the uterine mucosa (Chapter V) on the ninth day after ovulation 54 and 55). Hertig and Rock (1945) have shown that the human blastocyst is already partially implanted between the seventh and eighth day after ovulation
Polar Tpopwoblast Inner Cell Mass
Fig 33 A section of a g-day macaque blastocyst Four types of cells may be recognized, the blastocystic trophoblast, the polar trophoblast, formative cells of inner cells mass and endodermal cells, the zona pellucida has disappeared and the blastocyst IS ready to be implanted (Re-drawn after Heuser and Streeter, 1941 ) x c 240
Fig 34 — A three-dimensional reconstruction o the same blastocyst as in Fig 33 ^ ®
flattened endodermal layer is spreading in 0 the inner aspect of the blastocystic tropho as (Re-drawn after Heuser and Streeter, 194* ! X c 280
Blastocyst Stage and Formation of the Germinal Layers
For descriptive purposes the early development of the embryo may conveniently be subdivided into stages It must be emphasized, however, that normal development is a continuous process and that this subdivision is for descriptive purposes only The account which follows IS an attempt to provide a synoptic picture of early human development and is based on t e published descriptions of a large number of human embryos (see Appendix)
In most mammals, the morula, at the time ivhen, or just after, it has passed into the uterus, undergoes modifications which are chiefly of a physical character Fluid passes from the uterine cavity through the zona pellucida and outer cells of the morula, which act as a dialysing membrane, into the intercellular spaces between the centrally placed inner cell mass and the outer ce s ^Vith the increase in the amount of fluid the spaces on one side of the central cells become confluent forming a single cavity, the blastocoele, and the outer cells become flattened (Figs 32, 33 and 34) •
\s a result of these changes the inner cell mass comes to be attached etcentncall> to the inner aspect of the outer flattened cells \%hich are now called the trophoblast The embryo at this stage of development is referred to as a blasloeyst At about this time m most mammab and, as Hertig and Rock hav e recently found (Fig 35), also in man the zona pellucida disappears, thus permitting the trophoblastic cells of the blastocyst to become attached to the uterine epithelium (Chapter V and Figs 54 and 55) ^ . ov
The trophoblastic cells proliferate rapidly and invade the maternal tissue (Figs 3b and 5t5) In the monkey and presumably in man cndodemial cells segregate from the blastocoehc surface of the inner cell mass and become grouped into a single layer — the pnmary endoderm (Figs 33 34 and 36) The remaining cells of the inner cell mass which are at first intimatelv related to the overlying trophoblast constitute the columnar embryonic ectoderm (Figs 36, 37 and 38) As these latter cells arc the source of the embryonic ectoderm and in later stages, of the secondary mesoderm and may give rise to further endodenn, they have been called the formatiie cells (Heuser and Streeter 1941) Between these ect^crmal cells, which become arranged into
Fio 35 Photomicrograph of a secoon of a human bIastoc>st X 600 (Reproduced by the courtesy of Drs Ileriig and Rock J
Ftc 36 — \ section of a 7I day human ovum partially implanted m secretory endometrium X too The embryo is represented by the rounded mass of cells just above the trophoblastic mass and beneath the thin membranous pomon of the collapsed blastocyst wall (Reproduced by the courtesy of Drs Rock and Hertig )
a flattened disc, and cells {ammogemc) which arc denved from the covering trophoblast a cavity appears— the ammolic cautj (Figs 36 37 and 58} At the penphery of the disc the flattened amnjogenn, cells are directly continuous with the embryonic ectoderm In the youngest known implanted human embryo the amniotic cavniy has already appeared (Figs 36 37 and 58) Its further history is considered on page 78
During the period of the formation of the ammotic cavity the endoderm is concerned in the formation of a second and initially larger cavity — the pnmary jolk sac In the monkey blastocyst the endodermal cells spread beyond the maigins of the ectodermal disc (Fig 34) and by extension and proliferation come to line the whole blastocyst thus forming the pnmary yolk sac This yolk sac later becomes separated from the inner surface of the trophoblast by extra embrjomc mesoderm In the 7! day human blastocyst (Fig 36) the endodermal cells already form a single laver on the uterine cavity aspect of the fonname cells In slightly older human blastocysts (Figs 37 38 and 58) a primary yolk sac has appeared and a considerable amount ofloose extra embryonic mesoderm separates it from the inner aspect of the trophoblast (Figs 37, 38 and 58) The human yolk sac in these stages has a roof of cuboidal endodermal cells m contact with the
columnar embryonic ectoderm. The latter together with the cuboidal endodermal cells constitute the bilammar embryonic disc which is approximately circular in outline From this disc all the tissues of the embryo proper are derived The endodermal cells of the yolk sac roof are directly continuous at the edges of the disc with a layer of very thin mesothehal-hke cells m contact with the extra-embryonic mesoderm. This layer has been called the, e.'.ocoelomic, or Heuser's, membrane The precise nature and origin of the cells of this hning layer have not been determined They may differentiate in situ from the inner cells of the primary mesoderm or they may possibly be derived from the disc endoderm by migration as occurs in the macaque monkey (see page 75 for discussion) Whatever the nature of these cells, the cavity enclosed by them and the disc endodei m was called the exocoelom by Streeter (Fig 38) We,
pl'otomiciogiaph of a human implantation of estimated age 12 days (Hertig and oc ) t he syncy tiotrophoblast has irregular laminae containing some maternal blood e cytotrophoLiast consists of an inner irregular shell The -trophoblast at the abemP° ^ Ihtle differentiation and at one point is not yet covered with uterine
epi le lum The inner aspect of the cytotrophoblast is lined with mesoderm which is TOn ense on its inner aspect to form a membrane, the exocoelomic or Heuser’s membrane le em lyo consists of a thick layer of columnar embryonic ectoderm and a thinner layer o irregu arly arranged polyhedral cells, the embryonic endoderm, the latter, at its edge, is on muous 'vith the exocoelomic membrane The space lined by the exocoelomic memf ^ endoderm has been called the exocoelom by Hertig and Rock, in the present text le erre to as the primitive yolk sac A space, the amnion, lies between the mesoderm and embryonic ectoderm X c 100
however, shall call it the primary yolk sac (Fig 37). It ^vlll be seen that the cells of the primary
cuboidal cells in its roof (embryonic disc endoderm) , and flattened mesot e la - 1 e cells enclosing the remainder of the cavity Soon the cuboidal endodermal cells m a oca ize area near the future anterior margin of the embryonic disc become columnar This area of columnar endodermal cells is Xh^rochordal plate (Fig 39) ; it confers a bilateral symmeUy ^ ^ 6isc by establishing an antero-posterior axis The flattened cells limng the
remain er o t e primary yolk sac are concerned with the early nutrition of the embryo and they ° ^o'^tri ute to Its structure with the possible exception of early blood cells (Chapter V )
• ^ separating the primary yolk sac from the inner aspect of the trophoblast is ca e
the primary^ extraembryonic mesoderm (Fig 38), it is absent m the youngest known human embryo (Fig 35) but m slightly older ones fills the space between the trophoblast externally and e amnion an primary yolk sac internally This precociously developed primary extra-embryonic mesoderm m man and the higher primates appears to be derived from the trophoblast Such a derivation of extra embryonic mesoderm is unlike that found in most other mammals vvhere all the mesoderm arises from the ectoderm of the posterior part of the embryonic disc in the region ofthe Cnniitue xtreai (see Chapter XVI) .
In shghtK older human embryos the primary mesoderm has increased in amount and terms a loose mesenchymatous reticulum'^ the magma nhadatt Later small ca\ itics appear in the primary mesoderm these enlarge and become confluent to form the extra embryonic coelom except in an area v\ here the amnion remains attached to the trophoblast The mesoderm is thus separated into a layer lining the trophoblast and one covenng the sides of the amnion and the yolk sac
Fic 38 — \ schematic representation of Fig 37 based 00 a reconstruction b> Heriig and Rock The relationship of the embryo to the surrounding endometrium is shown X c 130
The primary mesoderm lining the trophoblast and covenng the sides of the amnion is called the extra embryonic somatopUurtc (panetal) mesoderm The part of the primary mesoderm covenng the yolk sac is called the extra cmhiyonic sphnchmpUunc (visceral) mesoderm * The membrane formed bv the extra embryonic somatopleuric mesoderm and the overlying trophoblast is known in mammals is the chorwn It corresponds to the serosa of reptiles and birds At this stage of development the amnion with the attached primary yolk sac is suspended from the inner aspect of the chorionic sac by that mass of primary mesoderm into which the extra embryonic coelom has not extended (Figs 39 and 40) This portion of the primary mesoderm will later become the connecting stalk
It IS important to realize that the extra embryon c splanchnopleunc (v isceral) and somatopleuric (parietal} mesoderm only cover or line the foetal membranes and play no part in the formation of the embryo The mesoderm covering the amnion for theoretical reasons u regarded as somatopleuric (Chapter \ I)
At the stage of development now reached (about the 1 2 th day) the embryo itself is represented by two apposed discs of cells — embryonic ectoderm and embryonic endoderm. The embryonic ectoderm forms the “floor” of the amniotic cavity and is continuous at its edges with the amniotic cells. These ectodermal cells as yet show no regional differentiation. The embryonic endoderm, on the other hand, forms the “roof” of the primary yolk sac It shows the localized thickening already referred to as the prochordal plate. There is as yet no evidence, in the embryonic disc, of the presence of a third germ layer (mtra-embryonic mesoderm) The next iinportant phase in development is a regional difiei entiation of the embryonic ectoderm to forma primitive streak and the derivation from it of this mtra-embryonic, or secondary, mesoderm
The Formation of the Primitive Streak, Intra-Embryonic Mesoderm and Notochordal Process
The primitive streak is an area of the to form a bilaminar membrane thcV/oarai mtnbtane (Figs 43 44 and 47) The primitive streak persists as m actuely proliferating area until about the ('i e , the end of the
somite) stage It then undergoes retrogressive changes and rapidly diminishes in size
NOTOCHORDAL PROCESS
As the intra embryonic mesodcrtti is extending forwards there is, at the anterior eKtrerrulv of the primitive streak a farther proliferation of the ectoderm known as Hensen s node or the /)rtmUiie i-not In the centre of this proliferation an invagination of the ectoderm (the blaslopore) occurs (Figs 43 44 Aiiti 4b) Thtc&M> sc D
of the invagination probabl> represents the blastocoelc (see Chapter XVI) of lower forms while its margins are comparable to the dorsal portion of the blastopore of such forms The pnmitn e streak itself is believed to be homologous to the lateral and ventral lips of the blastopore (See Chapter XVI for the phylotjcnetic significance of the blasto pore and Chapter VIll for its signi ficance m developmental mechanics )
In the mid line of the embryonic disc a cord of cells is budded forward from Hensen s node between the ecto derm and endoderm, this cord u known Mthtnotochordal otkead ^ro«Jf{Fig 43)
The anterior extremitv of the process comes into contact with the postenor edge of the thickened prochordal plate by this relationship the anterior end of the process becomes relatnel> fixed The invagination of the blastopore then extends into the notochordal process to form a cavity, i)M\/notochoTdal or archenUTtCi canal (Figs 43 and 44) As the anterior end of the notochordal process is relatively fixed further growth m length of this process is mainly brought about by the prolifcra uon of cells at Hensen s node which with the primitive streak migrate* or IS earned, m a caudal direction as the notochordal process and embryo increase in length
Fio 40 — A transverse section through the anterior p$n of the embijonie disc and related partof ihechononic vesicle
or the tdwjrds Jones Brewer embr^ ' '
A Riesoderma] <.ondensat(On i B Vdsculooenic space x c 200
r cmbr>o (after Bre\ er)
"" — "i connecting stalk
Meso*™ „ budded off from the sides of Hensen s node (Fig 49D) connnuous svilh that tvhtth ts domed from the rest of the pnntth.e streal The notochordal proeess now fuses with and becomeMWereatotd the eraboon.0 endodetm (F.gs 44 and 40B) r-Opemnirs appear m the floor of the notochordal canal tvhtch consequently commumcale yvith the toS
and Im’ Tb ■*"“ n o f '■rought tmo tommumcanon (F.gs 44 46
and 48) The open, ngs m he floor of the notochordal canal become confluent and a «ooy e .s foraied on the under surface of the notochonjal process Thts groove becomes sha 1 [ot,er
plate (Fig 49A) and as development proceeds it extends in a caudal direction, differentiating out of the notochordal process as this process elongates in association with the proliferation and backward migration of Hensen’s node. Thus the notochordal tissue, from the prochordal plate to the opening of the notochordal canal, instead of lying between the ectoderm and endoderm becomes temporarily intercalated in the endoderm so that it forms an axial stnp separating the embryonic endodeim in the roof of the yolk sac into right and left portions as far back as the notochordal canal As the embryo elongates the definitive notochord is
Fig 41 A transveise section through the posterior part of the same embryo as Fig 39, showing the primitive streak and early development of the intra-embryonic mesoderm
mesodeimal X c. 200
condensation in connecting stalk
developed from the notochordal plate by a longitudinal folding of the latter and Its separation from the endoderm This folding process commences cranially and progresses caudally as the embryo grows (Fig. 49). The endoderm, ivhich probably includes some remaining intercalated notochordal plate cells, then becomes continuous once more across the mid-hne as the definitive notochord separates from it (Fig. 50).
In an embryo at the time when the notochord is separating from the notochordal plate, three phases of notochordal formation can still be recognized (a) the proliferation of cells at Hensen’s node; {b) the intercalation of the cells into the roof of the yolk sac to form the notochordal plate; and (r) m the anterioi part, the separation of the cells from this plate to form the notochord There is thus an antei o-posterior gradient involved in the process.
By the fourth week, when the embryo is approximately 4 mm long, almost the entire length of the notochord IS in Its final position between the endoderm in the roof of the yolk sac and the ventral aspect of the neural groove, or tube, which has now formed from the overlying ectoderm. In the tail region, however, the same relations are still present as existed at Hensen’s node soon after the notochordal process appeared. The blastopore, which is now m the floor of the neural groove, persists as the dorsal opening of the r^otochordal (no^v called neurentenc) canal. The anterior extremity of the notochord remains attached to the endoderm for a long time (Figs 163 and 375) The further history of the notochord will be discussed in connexion wuth the development of the skull and vertebral column (Chapter XIII). ^
Intra-Embryonic Mesoderm
The intra-embryonic mesoderm arises, for the most part, by proliferation from the in that part of the embryonic disc known as the primitive streak (page 48). The priim
streak, ho\\c\er is not sold) concerned uith the formation of mesoderm for Heuser and Streeter (1941) have shown, tn the monke>, that the cells of this area of the enibr>onic disc arc primitive and plunpoUnttal and arc, therefore capable of givini, rise to further ectoderm or to endoderm Moreover, some
intra embryonic mesoderm as will q
be described more fuliv later arises
from ectoderm otlicr than that of the H^V
primitive streak (page 270) The \c^ *
mtra embryonic mesodermal cells
arising from the primitive streak pass -s/® 'X-A
laterally betvs een the ectoderm and
endoderm until they come into con 0 /)
,act ,u.h .he pr,mar> extra embr, <j]
onic mesoderm covenrlg the amnion \v
and yolk sac (Fig 49) The meso ^ I \o f c o u e
dermal cells also migrate forward I 1 / 9b“ « ^
into that part of the embryonic disc /fi/
which lies anterior to Hensen s node /iJ
and flank the notochordal process V\\
which has arisen from it A small ’ , , *^v \
amount of mesoderm mav also anse
from the sides of the notochordal %*
process (Hill and riorian 1931 and
others) \s the growth in lenctil of \ »chrmai.c ihrep dimmi t nsl reconstnjction
.1.- .,K 1 ,j»i ,.c, ^ of llie I dwaroj Jon« lires rr oiiim \ cut lUrface of primi
the notochordal process is accom tor streak It future ronnecunc stalk C margin of the
panied by a progressive caudal dis endoderm ofthermhryonre due a c aoo
placement ofthe primitiv c
streak the mesoderm pro
duced by the latter comes ^
to lie on each Side of the V^X /esv \ c
notochordal process This ^ ^
ectoderm and endoderm s — J P ^
of the disc except in the ^
mid line from Hensen s " '* **.. * *’
node to the anterior oT«e o e v r/
tip of the notochordal \ — _ ' ‘
process in the region of k—— ToftTrK^-^ iFc, , U
the prochordal plate and «
(in the later presomite /
embryos) in the region of ^ ^ \^|5
the cloacal membrane
With the formation
of the neural groove and |]'
the separation of the /" < u - fl*
definitive notochord from ^
the notochordal plate the p.e « -\^t.onrf rchemanc three d, men,. onal recoatiracon ofthe Hugo intra embrvonic mfsO embno ThrcoloursrhAmmn >hi> «;».<» rend ... i?.-. ..._j
intra embryonic mesO derm on either side of the notochord becomes
emboo The Mlour schemes m this figure and m Figs 44 and 47 are similar The nuclei of the «idodertn are shown in -yeUiyw of the notochordal process
m red ol the ectoderm and extra embryonic mesoderm in black andofihc mesoderm arising from the primiuve streak in blue X c qo
thickened to form a longitudinal mass known as the paraxial mesoderm This paraxial mass when traced laterally gradually thins into the lateral plate mesoderm It is this lateral plate mesoderm which becomes directly continuous with the extra-embryonic mesoderm beyond the margins of the disc
By the 21st day of development the paraxial mesoderm on each side of the notochordal process and, later, of the definitive notochord, becomes segmented into paired cubical masses called somites (Figs 50, 97 and g8). The first somite is formed a short distance behind the cephalic tip of the notochord and successive somites are progressively formed by differentiation from the paraxial mesoderm as it arises from the primitive streak. The first pair of somites to be formed in man and higher vertebrates are the first occipital; and each subsequent pair of somites lies immediately behind the previously formed pair No somites are formed in the mesoderm in front of the notochord. The paraxial mesoderm, however, extends forwards as far as the anterior end of the future brain plate as a diffuse mesenchyme The somites are
Fig 44 — A sectioned schematic reconstruction of the Rossenbeck embryo (Hochstetter, Pehl) Colour scheme similar to that in Fig 43 The notochordal canal now has several communications with the yolk sac The allanto-enteric diverticulum has grown into the connecting stalk where it is surrounded by mesoderm (A) derived from the primitive streak B — communication between notochordal canal and yolk sac C — cardiogenic area X c 50
somewhat triangular, on transverse section, with medial, ventral and postero-lateral walls (Figs. 50, 230 and 274) Each consists at first of epithelioid cells enclosing a somite cavity, the myocoele The myocoele later becomes occluded by the proliferation of the cells of its walls (Chapter XIV) Altogether 42-44 pairs of somites are formed in the human ytnbryo The lateral plate which, for the most part, remains unsegmented in man and higher vertebrates IS attached to the ventro-lateral angle of each of the somites by a continuous tract o mesoderm called the intermediate mesoderm (Fig 230) This intermediate mesoderm later undergoes changes which result in the formation of the excretory system and the gonads In front of the somite region the lateral plate mesoderm of each side extends forwards within the margins of the embry^omc disc and eventually fuses in the middle line in front of the prochorda plate which, with the overlying ectoderm, forms the bucco-pharyngeal membrane This latera plate mesoderm, of bilateral origin, m front of the prochordal plate is called the cardiogenic mesoderm as the heart later develops in this region.
Small isolated cas toes nosi appear on each side .n the hlerd mesoderm and soon hecorne .onfluent to form a single casit> the intra embrjonic coelom Tlie casitations extend fonsar on each side n .tlnn the embrvo until thex fuse aerosj the middle line in the cardiogenic mesoderm therebj forrains a single horseshoe shaped intia embryonic coelom
Tic. 45 — \ dra in^ of the dorsal aspret of a modfl of an i8da> prcsomite eml rso The letters \ B C D and r indicate the let els of the sections A BCD and F of Fig 49 x c Sj (After Heuser 193'’
FiQ 46 — \ drawing t f the \entnl aspect of the presomiie emlr>o illustrated in Iig 43 y c 53 (\fier Heuser )
Intra Emdryonic Coelom
Thts coelom is at first a closed space later hotsever, at the litcril edt'C of each of its caudal extremities itformsacommunicitionwilhthecxtra embryonic coelom (Fiqs 50 and 119) The cavity is lined by the intra embryonic parietal, or somatopleuric mesoderm m contact with the ectoderm and the mtra embrvonte visceral or splanchnopleunc mesoderm m contact with the endoderm The anterior portion of the intra embryonic coelom which passes trans versely across the middle line of the front part of the embryonic disc anterior to the bucco pharyngeal membrane is the pnmordium of the pericardium and has the cardiogenic plate (of splanchnopleunc mesoderm) m its floor (page 137). With the formation of the head fold and the resulting reversal of the head end of the embryo the pericardial portion of the intra-embryonic coelom is carried ventrally and caudally, and is also reversed so that the endothelial heart tubes arising from the cardiogenic plate now invaginate its splanchnopleunc roof (Figs, 83, 120 and 162), As a further result of growth changes m the anterior region of the disc the mesoderm (fused splanchnopleunc and somatopleuric) which initially was anterior
Fig 47 — A schematic representation of the germinal layers of the Heuser presomite embryo from the dorsal aspect Colour scheme as in Fig 43 In the upper half of the illustration (right side of the embryo) the ectoderm has been removed to show the extent of the mesoderm A window has also been made in the latter to show the underlying endoderm In two situations (prochordal plate and cloacal membrane regions) the ectoderm and endoderm are in contact X c 67
to the pencardium nou lies caudal to it and below the de\ eloping foregut This mass ol mesoderm is called the septum transiiTSum
Each dorso lateral angle of the pencardial ca\’it> is still continuous with the corresponding, caudalh directed limb of the intra embryonic coelom which passes dorsal to the septum transtersum on the side of the foregut As these limbs are communications between the pericardial ca\it> and that part of the intra embryonic coelom which will become thepentoneal
cavitv they are called the pmcardio-perUomal canals (Fig. 217). With the growth m length S the’foregut these canals become progressively longer and, soon each is invaginated from the medial aspect by the developing long bnd of the side concerned. The pericardio-pentoneal Sials can now be called the plmral cavtUes. Thus at this stage the whole intra-embn'onic “dom consists of a median pericardial cavity, two primitive pleural cavities and the peritonea cav ty The pericardial cavity communicates on each side with the corresponding pleural Sv!ty by way of a pericardio-pleural opening. Each pnmitive pleural cavity is m communiLtion by way of a pleuro-pentoneal opemng with the peritoneal cavity, the latter is Tfree commLcation. on each side of the yolk sac, with the extra-embryomc coelom.
In later development the pericardio-pleural and pleuro-pentoneal canals are obliterated and the pericardium and the two pleural cavities are completely separated from the peritoneal cavity (pages 218 and 220). Still later in development the peritoneal cavity itself becomes
NEURAL TUDE AMNJON
1930) X c 140
completely closed off from the extra-embryonic coelom at the umbilicus rsomato lesult from the subdivision of the original intra-embryonic coelom possess
pleuric) and a visceral (splanchnopleuric) wall The latter always forms cubdivision
organ which appears to he within any of the cavities The further deve opmen
of the coelom is described in Chapter X.
PROCHORDAL PLATE AND BUCCOPHARYNGEAL MEMBRANE
The prochordal plate is a circumscribed area of thickened embryonic en ° j jj,g
anterior part of the roof of the yolk sac This endoderm is in contac wi ^ ^
anterior part o: me rooi oi me yoiK sac xius vi,nrpss and
ectoderm, no mesodeim being interposed. The anterior tip of the Whei
ecioacnu, uu nicsuucini uemg, m-Li-i jjuavu. --x- nlfii-p When the
later the notochord itself, comes into contact with the posterior edge o e p • lateral plate mesoderm of each side grows forwards into the cardiogenic par o disc It skirts the periphery of the prochordal plate The prochorda p ate le gnt
same plane as the embryonic disc, but with the formation of the hea , pardiogemc of the anterior portion of the neural plate, and the caudal displacemen ° , .p 3^),
mesoderm, it comes to he in a plane at right-angles to the anterior end o e overlying
The prochordal plate now forms the anterior limit of the foregut and, toge er -membrane
ectoderm, with which it remains in direct contact, constitutes the buccop arynge
This membrane soon comes to be bounded on each side bj the deseloptng branchial mesoderm (see later) tihich bulges anteriorly so that the membrane lies m the floor of an ectodermal depression— the stomatodaeura, or pnmitne mouth In late somite embryos (Iig tot) the membrane breaks dow-n thereb> establishing contmuil) between stomatodaeum and foregut
In lower \ertebrates the cells of the endodermal prochordal phte are known to give ongin losoraeoftheintra embryonic mesoderm m the central region of the head These cells may also possess an organizing effect on the adjacent neural tissue The fate of the prochordal plate m
Fig 51 — \ draw n® of a trans>prscseciion through a 16 somite human embrvo at the level of the lit pharyngeal arch buccopharyngeal membrane and otic placode (after Bartel mezandLvans 19 C) X c 133 A — tangential cut through cranial lip of embryo
mammals can only be surmised from its history in these more primititely organized \eitebrates but there is good reason for considenng it to be an important developmental apparatus m all vertebrates
Cloacal Membrane
In early primitive streak stages there is an area at the posterior end of the embrvomc disc where the ectoderm and the endoderm remain m contact no intra embryonic mesoderm being interposed This is the primitiv e cloacal membrane The area of contact is at first characterized bv a thickening of the endodermal cells in this region the cells soon become flattened and together with the ovtrlyang ectoderm form the doacal membrane In the later presomite stages this membrane increases m size and extends backvtards on to the dorsal surface of the proximal part of the allanto-enteric diverticulum (Fig. 44). The mesodermal cells arising from the posterior part of the primitive streak pass backwards around the sides of the cloacal membrane to augment the mesoderm of the connecting stalk, but do not interpose themselves between the layers of the membrane itself,
At the time of its first appearance the cloacal membrane is situated posterior to the primitive streak and its ectodermal surface is directed dorsally. With the development of the tail fold and reversal of the posterior part of the embryo m the late presomite and early somite stages the cloacal membrane gradually comes to be situated on the ventral surface of the embryo (F igs 79, 83 and 144). With further growth of the tail the ectodermal surface of the membrane comes to be directed towards the developing infra-umkbcal region of the anterior abdominal wall (Figs 144 and 233). The original posterior margin of the membrane is now continuous with the caudal attachment of the umbilical cord. In later stages the development of the ge, ital tubercle and infra-umbihcal part of the anterior abdominal wall and the decrease in s )f ihe tail and post-anal gut cause the cloacal membrane to undergo a rotation m the reverse ( on so that it is directed posteriorly and downwards. With the development of the u)ou i ptum the cloacal membrane becomes subdivided into an anterior part, the urogenital i/iemium and i posterior part, the anal membrane (page 212). Later, as is described in fJli ip ei ^1, ihese membranes break down to give continuity between the cloacal derivatives and ill'" xieior
Tiip luiihc, history of the embryonic disc must now be delayed while the implantationi 01 r lie hi ."■toc' 't and the development of the foetal membranes are considered. The description ol the itf \elopment of the embryo itself is resumed in Chapter VII.
References
\llen, r r.wi I P , Newell, Q, U , and Bland, L J. (1930) Human tubal ova, related corpora lutea and
ut I' lubui! Contrib Embryol , Carnegie Inst. Wash, 22 , 45-76
Blandae 1 i me’ Money, W L (1944) Observations on the rate of transport of spermatozoa in the female
!tei . 1 u let of the rat Anat Rec , 90 , 255-260
Bo\d, J I' Hirnilton, W J,, and Hammond, J , Jr (1944). Transutenne (“internal”) migration of the o\u m sheep and othei mammals J Anal, Land, 78 , 5-14.
Biewer, J I ( <9381 A human embryo in the bilaminar blastodisc stage (the Edwards-Jones-Brewer o\um) Contrih Embryol, Cmnegie Inst Wash, 27 , 85-93.
Cary, W H (1936) Duration of sperm cell migration and uterine secretions J Am Med Assoc, 106 , 2221-2223
Chang, M C {igsD Fertilizing capacity of spermatozoa deposited into the fallopian tubes Nature, 168 , 697-698
— and Pineiw, G ^951) Physiology of fertilization in mammals Phys /?w , 31 , 1-26 Corner, G \\ • 1932! Cytology of the ovum, ovary and fallopian tube Special Cytology (ed Cowdry),
2nd ed , pp 1567-1607 Hoeber, New York
Florei, H , and Walton. A (1932) Uterine fistula used to determine the mechanism of ascent of the spermatozoon in the female genital tract J Physiol , 74 , 5-6 {Proc Physiol Soc )
Florian, J (1933) The early development of man, with special reference to the development of the mesoderm n membrane J Anat, Land, 67 , 263-276 a h ,1
Gerard, P (1932) Etudes sui I’ovogenese et I’ontogenese chez les Lemuriens du genre Galago Arch ae Biol , 43 , 93-152
Hamilton, W J (1934) The early stages in the development of the ferret, fertilization to the formation of the prochorckl plate^ Trans Roy Soc, Edin , 58 , 251-278
U 944 ) Phases of maturation and fertilization in human ova J Anat, Land, 78 , 1-4 (1949) Early stages of human development Ann RCS Eng, 4 , 281-294 Hamrnond, J. (1925) Reproduction in the rabbit Oliver & Bovd, London
~ (1941) Fertility in mammals and birds Biol Reviews, 16 , 165-190 , p ,
Hartm^, C G {1933) On the survival of spermatozoa in the female genital tract of the bat Qjiart ne 5101,8,185-193 F 6
and Ball, J (1930) On the almost instantaneous transport of spermatozoa through the cenix an uterm of the rat Proc Soc Exp Biol and Med , 28 , 3 12-3 14 Hertig, A 1. (1935) Angiogenesis in the early human chorion and in the primary placenta of the macaq nmnkey Contrib Embryol , Carnegie Inst Wash , 25 , 37-82 i pn
° I ^*941) Two human ova of the pre-villous stage having an ovulation age of about eiev ^ J '"t respectively Contrib Embryol, Carnegie Inst Wash, 29 , 127-156 and Rock, J (1945) Two human ova of the pre-villous stage, having a developmental age of abputse respectwely Contrib. Embryol, Carnegie Inst Wash, 31 , 65-84 and Rock, J. (1950) Personal communication
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Hamilton WJ. Boyd JD. and Mossman HW. Human Embryology. (1945) Cambridge: Heffers.
Cite this page: Hill, M.A. (2024, April 18) Embryology Book - Human Embryology (1945) 4. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_(1945)_4
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