Paper - A Human Ovum at the Previllous Stage

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The specimen which is described in this communication consists of what is believedtobeanormalovum thathasbeennotlongimbeddedintheuterus, and it represents the youngest stage of human development that has so far beenrecordedinthiscountry. Itwasdiscoveredbyoneofus(J.H.D.)during the course of a post-mortem examination of a woman, aged 28, who had died from internal hydrocephalus due to fibrous adhesions at the base of the brain which were probably the result of trauma. The post-mortem examination was made not more than ten hours after death, and there is no reason to suppose that the specimen is not normal.

A large corpus luteum was seen in one ovary and this directed particular attention to the uterus; on opening this along the anterior wall the mucous membrane was found to be thick and velvety, and on the posterior wall, towardsthefundus,therewas seenasmallvesicle(Fig.1)projectingabove the surface which was thought to be an early ovum. A small wisp of fibrinous materialwasadherenttothesummitofthevesicle. Nomenstrualhistorywas available.

The opened uterus was fixed in formalin and, after being photographed, a blockoftissuecontainingthevesiclewas removed, cut at 4p,and stainedwith iron-haematoxylin and eosin; blocks of tissue from other parts of the uterus were also removed for study of the structure of the endometrium at a distance from the vesicle; this endometrium presents the characters typical of the premenstrual phase, with large, tortuous and active glands, and a rich blood supply;thesectionsshow,too,thatthefixationandpreservationaregood. In thesectionsoftheblockoftissuecontainingthevesiclethemucous membrane is5mm. thickandisdivisibleintoastratumcompactum,03 mm. thick,and a stratum spongiosum (Fig. 2).

The implantation site can be recognized in the sections with the unaided eye by the pink stain which has been taken up by some dilated glands lying atthebaseofthearea. Contrarytowhathasbeenfoundinseveralyoung specimens, and to what might have been expected from the appearance of the intact vesicle, the implantation site is not much raised above the surface in the sections. Implantation has occurred between the mouths of two glands which are bent round the ovum, and the site of implantation occupies the stratum compactum only. The ovum isnot covered with a decidua capsularis, and the point of entry of the ovum into the endometrium is seen (Figs. 5, 7) as a crater-shaped area, from which the uterine epithelium is deficient, over- lying the summit of the ovum. The aperture of entry is 0-23 mm. wide; it is filed,as with a bung, by the 'operculum' (Teacher, 1924) and iscapped by the 'closing coagulum' or 'Gewebspilz' (Peters, 1899). The latter appears as a loose mass of fibrinoid material containing some leucocytes and it was seen as the small wisp, referred to above, when the uterus was opened.

The ovum (Fig. 3) consists of a slightly flattened chorionic vesicle, the blastocyst,whichhasaninternalmeasurementof047mm. intheequatorial plane, i.e. from side to side, and of 0'28 mm. in the polar plane, i.e. from the surface inward. The inner surface of the blastocyst is smooth and has the embryonic rudiment attached at its base; the outer surface is irregular owing to cellular and syncytial processes growing out from it into the implantation cavity. These processes are stained deeply with haematoxylin and they stand outinsharpcontrastwiththeclearcavityinwhichtheylie(Fig.4).Thesmooth inner surface of the blastocyst is lined with primary mesoderm, and inside this there is the exocoelomic vesicle (Heuser, 1938) enclosed by the exocoelomic membrane (Heuser's membrane). The embryonic rudiment is composed of a thick ectodermal plate which forms the ventral wall of the amniotic cavity, and of a rather thinner entodermal plate which is continuous at its margins with the exocoelomic membrane. There is no yolk sac.

There are no chorionic viliand thus the specimen belongs to the group of ova at the previllous stage, which includes the Miller (1913, and Streeter, 1926), the Kleinhans (Grosser, 1922), the Muller (1930), and the two new Hertig ova of which a preliminary account only has so far appeared (Hertig & Rock, 1939). Further, it corresponds with Streeter & Wislocki's (1938) stage II for the macaque, which they term the 'stage of trophoblastic lacunae' andwhichtheyestimatetobelongtotheperiodfromthe11thtothe14thday. The implantation cavity appears (Figs. 4-6) as an almost empty, clear and circumscribed area and thus stands out in sharp contrast with the adjacent endometriumontheonehandandthedarklystainedtrophoblastontheother; it is this character of the implantation cavity which gave to the specimen a cystic appearance when first seen in the uterus with the unaided eye.

Thetrophoblast. Growingfromtheoutersurfaceoftheblastocystarethe trophoblastic processes. In the account which follows, the terminology employed by Ramsey (1938) in her description of the Yale embryo will be used. Thus we are able to recognize central cytotrophoblast, peripheral cytotrophoblast, and plasmoditrophoblast or syncytium.

The central cytotrophoblast (Figs. 7, 8) forms the true wall of the blasto- cyst; it is composed of a single layer of lining cells which, for the most part, appear rather condensed and flattened and have darkly stained, round or oval nuclei, but poorly defined cel walls; in some sections the nuclei are packedcloselytogethergivingadarkbordertotheblastocyst,whileinothers, particularly in the region of the operculum, they are few and far between.

The peripheral cytotrophoblast (Figs. 4-8) appears as sheets, or columns, ofcellsgrowingfromtheblastocystwallintotheimplantationcavity;inother words, it is an extension outward of the central cytotrophoblast. The cels are larger and have more clearly defined walls than have those of the central cytotrophoblast, their nuclei generally are not so darkly stained, nor do they filthecelltothesame extent,sothatthereisoftenaclearspaceleftbetween the nucleus and the cel wall. Beyond the peripheral cytotrophoblast, and alsoextendinginamongst itscelcolumns, aregrey,filmymasses and strands whichmay benucleatedornon-nucleated;thistissueistheplasmoditropho- blast,orsyncytium(Figs.5-8). Itisdevoidofanycelboundaries,andin some places nuclei occur in clumps, like the 'heaped-up epithelial nuclei' describedbyStreeter& Wislocki(1938).

In the plasmoditrophoblast brown granules are seen in many places; similar granules have been described by Johnstone (1914) and Greenhill (1927). Johnstone suggested (p. 270) that they are composed of molecules of blood pigment adherent to a minute droplet of fat, the fat itself having disappeared inthecourseoftheprocessoffixationandstaining.We areofopinionthat this pigment is a formalin-haemoglobin precipitate, and the fact that it is found mostly at the implantation site and in the cells of distended glands which form lacunae of blood rather supports this view, since these are sites of haemorrhage, and it is well known that in slightly autolysed tissues such precipitates are common in histological material. The ovum, and the autolytic ferments present in the trophoblast, may well be responsible for some degree oflocalautolysis. Greenhillimplies(p.340)asimilaroriginofthegranulesin hisspecimen. Ithasnotbeenpossibletomakeanymicrochemicalanalysis of these granules as it would have involved an interruption in the series of slides,butitmay bementionedthattheyareanisotropic,asaretheformalin precipitates. The frequent occurrence of these granules in association with leucocytes provides further support for their origin from blood.

Several authors have referred to the foam-like condition of the syncytium of early stages due to the presence of innumerable vacuoles of various sizes, and the general opinion seems to be that this vacuolated syncytium has been derivedfromamoresolidplasmodiumwhichhasgrownoutfromtheblastocyst wall. Thus Bryce (1908) suggests (p. 43) that the spun-out condition of the plasmodiumorsyncytiumisduetotheformationinthevacuolesofadigestive fluid which, after rupture of the vacuoles, is replaced by maternal blood; the large amount of blood in the implantation cavity is a striking feature of the ovum T.B. 1. Streeter (1926), in his account of the Miller ovum, describes the lacunae as being small near the wall of the ovum and larger as the periphery is approached, and he refers to them (p. 37) as representing the 'histological picture of a process by which a solid mass of trophoblast becomes converted into a sponge-like syncytium'. The Miller ovum shows a lesdefiniteimplantationcavitythanthepresentspecimen.

In our ovum the vacuolated network (Figs. 7, 8) seems to be made up largelyofcoagulatedproteinwithbranchingcellsscatteredthroughit;thesecells appeartobepartlytrophoblasticandpartlystromal,andsomearedegenerate. This appearance isno doubt produced, so far as the protein is concerned, by fixation, and it seems probable that in life the contents were mainly fluid or gelatinous with strands of fibrin, amongst which the cells of the trophoblast were growing out from the blastocyst as in a tissueculture. We believethat our ovum, the Miller ovum, and the ovum T.B. 1, show progressive stages in the dissolution of the originally more solid plasmodium, the present specimen being at a stage intermediate between the Miller ovum, and the ovum T.B. 1, wherethevacuoleshavebecomefiledwithblood.TheMullerovum we believe tobeatastagesimilartoours.TheembryoKleinhans,judgedbythecondition of the implantation cavity, seems to be at a stage intermediate between the present specimen and the ovum T.B. 1, for it shows a cavity which is fairly clearcutbutwhichcontainsrathermorebloodthanispresentinourspecimen. By the same criteria, the two new Hertig ova are both at stages earlier than either the present specimen or the Miller ovum; Hertig's no. 7700 in particular shows an almost solid plasmodium surrounding the trophoblast wall.

Teacher (1924) refers to the two generations of syncytium, the destructive and temporary syncytium-the 'Implantations-syncytium' of Grosser-and the permanent syncytium of the chorionic villi-the 'Zotten-syncytium' of Grosser. Itisthisfirstgenerationofsyncytiumthatwehavebeforeus,and we get the impression that itshows evidence of destructive action and also of beinginaprocessofdegeneration,foritisadegeneratetissueandyetitseems able to open into capillaries and, contrary to what Streeter found in the Miller ovum, into glands also. Streeter further stated that he was unable to find any evidence of destruction or ingestion of the stroma cells by the syncytial loops; inthepresentspecimen,asserialsectionsareexaminedfromthenon-implanta- tion area towards the blastocyst, the first change seen is that the stroma becomes oedematous, the spaces between the cels are increased, and their nuclei become enlarged and paler. By the appearance of their nuclei these maternal stroma cels can be distinguished from the cels of the trophoblast, and in sections through the periphery of the implantation cavity they can be recognized without any doubt, though they are not numerous and their period of survival would appear to be short; here and there they can be seen lying in a mass of the filmy grey tissue that has been recognized as syncytium.

It may be suggested here that much of the lacy, network-like, appearance ofthetrophoblastseemstobeduetodestructionofitscels,by autolysisor by extracellular digestion, or by a combination of both processes; the general picture suggests the presence of some rather active ferment, or of conditions causing autolysis. We believe that many of the spaces between the tropho- blastic branches may contain autolysed blood, the more so because the red celsinmany ofthecapillariesinthevicinityareautolysed,thoughnot inthose fartheraway. Thisinterpretationisinconformitywiththesuggestionwe made aboveconcerningtheoriginofthepigmentedgranules.Thus, there does seem to be evidence of the digestion of the stroma cels by the syncytium in this specimen, and we believe that such destruction must have been extensive, for there islitleevidence ofthe stroma having been simply pressed outward, as Streeter found to be the case in the Miller ovum, though in some places it is arranged more or less in concentric lamellae as if it had been pushed aside to someextent. Itdoesseemthatthemainmethodofenlargementofthecavity, withthenecessaryremovalofthestromacels,isbyaprocessofoedemaofthe stroma,degenerationofitscelsandtheirautolysisordigestion. Itisnote- worthy that there is a strip-the 'border-zone'-of degenerated and necrotic stroma alround the implantation cavity, except where itisin contact with a gland (Figs. 4, 5).

The implantation cavity

The implantation cavity measures 1-0 mm. in its equatorialdiameterand0575mm. initspolar.Ashasbeenmentionedabove, it appears as an almost empty, clear and circumscribed area, and though this character of emptiness is an appearance only, yet in this character and in the sharpoutlineofthecavitythespecimenshowsaconditiondifferentfromwhat is found in other early ova, with the exception of that described by Muller, in that these have an implantation cavity more or less filedwith blood, and with an irregular and indefinite outline. The cavity rests on two glands which havebeensogreatlydistendedwithbloodthattheirepitheliumhasbeenquite flattened and resembles the endothelial lining of a blood vessel, for which it was at first mistaken (Figs. 3, 5 and 8). The distension affects mainly the deeperpartsoftheglands.Brewer (1937)statesthatinalhuman pregnancies reported there is an accumulation of blood in the uterine glands, and, in the Edwards-Jones-Brewerovum whichhedescribes,theglandsarecertainlyvery distended with blood, but the only specimen besides the present one that shows a comparable distension is that described by Herzog (1909). As to the cause of the distension in the present specimen, it is clear that in the case of one gland at least it is due to the fact that it does not open on the surface, its lumen being occluded with syncytium and its mouth incorporated in the implantationcavity. Itisthereforedistendedinpartwithblood,andinpart withitsownsecretionwhichhasnoexit. Inanothercase,theglandhasburst on to the surface (Fig. 6) and its contents have been expelled into the uterine cavity where they form a wisp of fibrinous material impregnated with leucocytes.

The closing coagulum and the operculum

A wispoffibrinousmaterialhas been alluded to already as the closing coagulum which caps the aperture of entryoftheovum intotheuterinemucousmembrane(Figs.1,3,5,7and8). The structure of this coagulum and of the contents of the implantation cavity isessentiallysimilar,anditmay beregardedasapartofthecontentsofthe cavity which has become free on the surface owing to the absence of any deciduacapsularis,andtothedisappearanceoftheuterineepitheliumoverthe point of entry of the ovum. The closing coagulum is also continuous in part with the contents of the gland which has burst on one side of the ovum. The very thin covering of the ovum was recognizable in the intact specimen, for theovum hadtheappearanceofatinycyst,likeablisterinthethickmucous membrane,withitspoleglisteningthroughthethincovering. Itisinteresting to note, in connexion with the origin of the closing coagulum, that Brewer (1937) showed a much larger and more organized 'blood clot' overlying the surfaceepitheliumattheimplantationsite,andhesuggestedthatitscharacter indicated previous bleeding into the uterine lumen; the implantation cavity in Brewer's ovum contains a good deal of blood, and this may explain the difference in the appearance of the closing coagulum in his specimen and in ours.

Theimplantationcavitydoesnotsurroundtheovum completely,forinits superficial part it is interrupted by the presence of the operculum (Figs. 2, 5). As so well described by Schlagenhaufer & Verocay (1916), quoted by Teacher (1924, p. 179), the operculum, 'as the stopper of a bottle, as the keystone of a vault.closes the entrance to the implantation cavity with its precious contents'. Itisclearlyanoutgrowthofthecentralcytotrophoblastatthe superficial pole of the ovum, and it fils the space between this part of the ovum andtheuterinecavity. Instructureitisliketheperipheralcytotropho- blast of the rest of the ovum, except that it is rather less cellular and more vacuolated; in it are some small masses of syncytium and a few degenerated maternal stroma cels.The whole mass has a degenerated appearance and gives the impression of being a tissue, derived from proliferation and outgrowth of the cytotrophoblast, which has nearly outlived its usefulness. In some sections(Fig.8)theoperculumandtheclosingcoagulumarecontinuous. Over the aperture of entry the uterine epithelium is deficient (Figs. 5, 7). Farther laterally it forms the sides of the crater-like area occupied by the operculum, butbothhereandintheadjacentglandsitisflattenedandhastheappearance ofhavingbeenstretched.Thisisquiteunliketheappearanceoftheepithelium lining the uterus and the glands generally, which is columnar.

The blood vesels

Fig.9 is a photograph of asectionthroughthemiddleof theovum,andonithavebeenmarkedwithinkalthebloodvessels. Itshows thattheendometriumiswellsuppliedwithblood. Small,thick-walled,spiral arteries and larger and thinner veins are seen in the stratum spongiosum, but capillaries only are present in the stratum compactum. There is no definitive blood sinus at the base of the ovum, such as is described by von Mollendorff (1921a) in the embryo 'Sch.', and by Ramsey (1937, 1938) in the Yale and Lockyer embryos; instead, there are numerous small vessels round the implantation site which ultimately join into two main veins, one rather larger than the other. The capillaries of the stratum compactum are opened by the syncytium and become incorporated in the implantation cavity, giving rise, at least in part, to the clear spaces of the cavity.

The embryonic rudiment

Theembryoisfoundontheinnersurfaceofthe basalwalloftheblastocyst. Itconsistsofathickectodermalembryonicplate which forms the ventral wall of an otherwise thin-walled amniotic cavity, and of a rather thinner entodermal plate which has not yet differentiated into any partofadefinitiveyolksac. Spreadingoutfromthesidesoftheamniotic cavity are the cels of the primary mesoderm which, when traced in a lateral direction, form a continuous lining for the inside of the blastocyst (Figs. 7, 8, 10 and 11). Within this primary mesoderm there is an even thinner layer (Figs. 5, 7 and 8), the exocoelomic membrane (Heuser, 1938); this encloses a large, more or less spherical, cavity which we thought at firstwas the yolk sac, admittedly a good deal larger than we had expected to find in an ovum at this stage. This membrane will be referred to in more detail after the other parts oftheembryohavebeendescribed. Itisunfortunatethatanumberofsections containing the embryo have been lost and it is thus not possible to make a completereconstruction,butthefollowingarethemeasurementsoftheembryo taken in the middle of the ten sections in which it occurs:

Cite this page: Hill, M.A. (2020, January 18) Embryology Paper - A Human Ovum at the Previllous Stage. Retrieved from

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