a human embryo with head-process and commencing archenteric

JOURNAL OF ANATOMY

A HUMAN EMBRYO WITH HEAD-PROCESSAND COMMENCING ARCHENTERIC CANAL

BY THE LATE PROFESSOR PETER THOMPSON, M.D.,University qfBirmingham; Fellow of King's College, London,

AND JAMES C. BRASH, M.A., M.D., B.Sc.,Professor ofAnatomy, University of Birmingham1.

TOWARDS the end of the third or beginning ofthe fourth week, and immediatelypreceding the formation of the neural groove, the human embryo passes througha phase of development characterised by the presence of certain axial structures,viz. the primitive streak, a head-process canalised by a rudimentary archentericcanal, and the protochordal plate. Even to-day but few examples of thisstage are on record, and Grosser, who has published an interesting account ofa young human ovum which showed these structures with great clearness,claims that previous to 1913-the date of his own publication-a similar stageof development in man had not previously been recorded. In 1918 Ingallspublished an account of a human embryo, somewhat less advanced in develop-ment, but strikingly like the preceding in all the essentials. A third examplewas recorded by Strahl in 1916, but up to the present2 the publication doesnot appear to have reached this country. Ingalls refers to it very briefly, andstates that it shows a very similar stage of development, and adds that no dataare given as to the age of the specimen.

The present paper is a further contribution to the subject, and, as far as canbe ascertained, these four specimens comprise the material which illustrates aphase of development in the human embryo which falls somewhere betweenthat represented by the ova of Fetzer, von Herff and Beneke on the one hand,and that represented by the ova of Frassi and Eternod and Graf Spee's Gleon the other. Estimating the age from the stage of development, Grosser gives18 days, which is perhaps not far out. This archenteric stage, if such a termmay be used for convenience, appears to be quite a transient one, and this mayaccount for the small number of specimens which up to the present have beendescribed.

The stage appears to correspond very closely with that which Wilson andHill have described in their well-known work on monotreme development asthe "post-gastrular stage." They point out that this stage "includes the de-

1 The clinical history of this embryo was detailed by the late Professor Thompson in hisIngleby Lecture before the University of Birmingham, in October, 1918. The first part of thispaper, including the "General description of the Ovum," he left in MS., and it represents all thathe was able to complete for publication before his lamented death.-J. C. B.

2 This was written in 1920.-J. C. B.Anatomy LVI 1

Peter Thompson and James C. Brash

velopment, from the primitive knot, of the so-called 'head-process' togetherwith various other phenomena associated with this, either causally or con-temporaneously. This phase of development is deserving of special recogni-tion," they say, "as constituting a new era, for, with its onset, the process of'notogenesis' is initiated, and the proper axis of the future embryo (Minot's'primitive axis') is laid down." A full description of the axial structures inour embryo will be given at a later stage. In the first place it will be moreconvenient to set forth the details of the clinical history, which have beenobtained with great care and are practically complete.

CLINICAL HISTORY, ETC.

The ovum was removed from the uterus of a married lady by Mr BeckwithWhitehouse, F.R.C.S., on account of the serious condition of the patient'shealth. It came into my hands on the following day, intact, and enclosedwithin a capsule of decidua. The following notes taken by Mr Whitehouseaccompanied the specimen.

The patient, Mrs X, was seen in consultation on December 3rd, 1917. Shewas of a neurotic and highly sensitive disposition, and had suffered fromnephroptosis, for which she had consulted a surgeon a short time previouslywith a view to an operation for its relief. Pregnancy, however, had super-vened, and this fact, together with the knowledge of the pending operation,produced an exacerbation of the mental symptoms, and suicidal tendencieswere exhibited. After full consultation it was decided to explore the cavityof the uterus and terminate pregnancy if such really existed.

The catamenial history had previously been quite regular-menstrualcycle 28 days. The last period began on October 25, 1917, and ended onNovember 1. No menstrual period occurred as expected on November 22.The husband, who had been away from home, returned on November 2, andcoitus took place on the evening of November 6. Mr X left Birmingham onthe morning of November 7, and no further coitus occurred. (The coitusprevious to that of the evening of November 6 took place some time beforeOctober 23, the day on which the husband left on a business journey for SouthWales, but how long before is uncertain. That no coitus took place betweenthese two dates, i.e. October 23 and November 6, forces us to the conclusionthat a previous cohabitation may be definitely rejected as a possible factor inthe case.)

Three days later, i.e. on November 9, the patient complained of pains inthe breast, and thought that she was pregnant.

On December 3, upon examination under an anaesthetic, the body of theuterus was found to be somewhat globular in shape and very slightly enlarged.No softening of the cervix or other sign of pregnancy was present. However,taking into consideration the very slight increase in size of the organ, it wasthought that a pregnancy might be present, and the uterine cavity was exploredat 4.30 p.m.

2

Head-Process and Commencing Archenteric Canal

The cervix was dilated by means of Hegar's dilators, and a blunt curettewas introduced into the cavity of the organ. Presupposing that the ovum wassituated either at the fundus or on the posterior wall, curettage of this areawas performed first. A small ovum was removed intact from the posteriorwall and placed immediately in a 10 per cent. solution of formalin. No chori-onic villi were observed, and the ovum appeared as a small disc-shaped vesicleabout half an inch in its greatest diameter. A small quantity of decidualtissue was also removed by means of the curette from the anterior and lateralwalls of the uterus. The cavity of the organ was then packed with gauze.

From a perusal of the medical history given above, and from data suppliedto Mr Whitehouse and myself by the patient and her husband, both of whomrealised the importance of exact statement, it seems certain that fertilisationmust have taken place after and was presumably effected by coitus on thenight November 6-7, 1917. It should be stated that the husband of Mrs X isa well-educated man occupying a professional position in the commercial lifeof Birmingham, and the history detailed above can, in my judgment, be im-plicitly relied upon.

THE AGE OF THE SPECIMEN

Before entering upon a description of the embryo and its adnexa, some-thing must be said regarding that most difficult problem, the age of thespecimen. In our case we are in the fortunate position of knowing most of theessential facts, and yet the difficulties of arriving at a trustworthy conclusionwithin narrow limits are practically insuperable. Without a knowledge ofsuch essential facts, the estimation of age is mere guesswork; with them weshall at least be able to arrive at an approximate estimate.

Moreover, from the standpoint of the history of the case, it is difficult tosee how, under the circumstances, any additional or more reliable data couldhave been obtained, which would enable us to calculate the age with completeconfidence. The really vital unknown factor is the day of the menstrual cycleon which the ovum was set free, and the absence of this knowledge is thebarrier which hinders us in working out the problem with any degree ofexactness.

The ovum was obtained thirty-nine days from the beginning of the lastperiod, thirty-two days from the end of the period, eleven days from theomitted period, and twenty-seven (nearly) complete days after cohabitation.Assuming that an ovum was awaiting fertilisation, and allowing twenty-fourhours for its occurrence, the absolute maximum time occupied by develop-ment was twenty-five or twenty-six days.

The fertilising coitus took place on the thirteenth day of the menstrualcycle, and sixteen days before the next expected but missed period. Thesedays may well have been taken up by fertilisation, time consumed in travellingdown the tube, the inhibition of menstruation, and the early stages of imbed-ding. In that case the ovum would reach the mucous membrane of the uterus

1-2

3


towards the end of the menstrual cycle, that is to say, at a period well adaptedto its nutritional requirements.

This leaves about twelve days from the time of the imbedding of the ovumto the termination of pregnancy by operation on December 3. Bryce andTeacher allowed seven days after implantation for the further growth anddevelopment of the young ovum described by them in 1908, and consideringthat our ovum is much more advanced in development, the additional fivedays seems a reasonable allowance.

But are the assumptions which we have had to make regarding ovulationand fertilisation justified in the present case? Certain considerations, whichmust next be advanced, seem to show that they are not, and that a period ofsix or seven days must be deducted if, on the ground of the degree of develop-ment, we assign our ovum to its appropriate place in the third week of thechronological tables of young ova compiled by Bryce and Teacher, Keibel andMall, and Grosser. For, as everyone admits, it is necessary, in attempting toascertain the age of a young ovum, to consider factors other than those avail-able in the obstetrical history of the case, and particularly the stage of develop-ment reached. Age and stage of development by no means always run parallel.For example, Keibel found in the pig differences which he regarded as equalto twenty-four to forty-eight hours' growth at such an early date as thefourteenth day of pregnancy. Nevertheless, any marked discrepancy betweenthe stage of development and the estimated age demands careful scrutiny.

Now the stage of development in the ovum under discussion approximatesto that found in the ova of Grosser and Ingalls, both of which have been esti-mated to be eighteen or nineteen days old, and is undoubtedly earlier thanthat shown by the ova of Frassi, Eternod, Delporte and Graf Spee's Gle, allof which have been placed at the end of the third week (nineteen to twenty-one days). True, amongst the six cases just noted, two only (Eternod's andDelporte's) have a clinical history comparable as regards fullness of detailwith our specimen, but if, on the ground of the clinical history, it be main-tained that ours is about a week older than the stage of development suggests,then a place in the fourth week in the chronological tables mentioned above,in company with His's Lg. and BB., would be incongruous.

Further, if the age of our ovum be estimated at eighteen to nineteen dayson the ground of anatomical findings, then fertilisation occurred on thetwentieth to the twenty-second day of the previous menstrual month. Sucha date would harmonise with the observations of Frinkel on ovulation, which,based on one hundred and thirty-three laparotomies, go to show that ovulationoccurs in the second half of the intermenstrual period, i.e. between the elevento twenty-six days from the beginning of the last menstrual period, with anaverage of eighteen or nineteen days. In other words, ovulation would haveoccurred about one week after the fertilising coitus of November 6.

This would call for a sojourn of the spermatozoa in the Fallopian Tube ofat least a week, a period during which it is reasonable to suppose they can

4


retain their fertilising power. Triepel has adopted a method of estimating theage of embryos based on the work of FrAnkel, which consists of subtractingeighteen from the number of days reckoned from the beginning of the lastperiod to the day when the ovum is obtained from the uterus. In our case,39 - 18 = 21 days, which is quite a good result.

It will now be advantageous if we place here for purpose of comparisonthe essential points in the histories of the three ova most closely related toour own:

FRASSI'S ovuM. This ovum was obtained at an operation for total extirpationof the uterus on account of persistent menorrhagia due to metritis, forty-twodays from the beginning of the last menstruation. Triepel estimates the age as42 - 18 = 24 days; Bryce and Teacher estimate the age to be eighteen ornineteen days; Frassi himself describes it as being less than ten days, whilstthe age reckoned on the basis of the stage of development is nineteen days.Such a result is a striking commentary on the danger of trying to narrow downtoo sharply the age of very young ova.

INGALL'S OVUM. This ovum was obtained thirty-four days from the begin-ning of the last menstrual period, as an abortion. Intercourse took place four-teen days previous to the abortion, and (doubtfully) also two weeks furtherback. Triepel's method would give an age of about sixteen days, whilst theage on the basis of development would be nineteen days. Ingalls himselfestimates the age at seventeen or eighteen days, but he states that he couldnot bring himself to look upon this figure with any degree of confidence.

GRossER's OVUM (KL. 13). This ovum is younger than that of Frassi, andaccording to Triepel's method the age works out at eighteen or nineteen days.It was obtained as an abortion from a healthy uterus after an operation forremoval of an ovarian cyst, thirty-seven days from the beginning of the lastmenstrual period. Owing to the irregularity of the menstrual cycle in thiscase, any estimate of age based on Triepel's method is likely to be misleading.

Therefore, from a perusal of these cases and others, one comes to the con-clusion that the estimation of the age of young ova, now assigned to the thirdweek, is a matter of approximation only, and it may be that in the future theage of some of them may have to be raised several days. For the present wemust not be dogmatic. We shall go further and do more good if we stronglyemphasise the approximate nature of our results. The problem under con-sideration is not one which can be solved with mathematical exactness, or byexperiment, or by presentation of the unbroken chain of connected evidence.

To sum up, the main points in connection with the age of our ovunm are:(1) The stage of development, which would indicate an age of eighteen or

nineteen days. This estimate must be very uncertain on account of thevariability of time taken in travelling down the tube. According to Grosser,the error may, in extreme cases, be as much as four or five days.

(2) The obstetrical history, which gives a maximum time of developmentof twenty-five or twenty-six days. If, however, an interval of some days

5


occurred between insemination and ovulation, then this figure is correspond-ingly reduced, and (1) and (2) are brought more into harmony.

(3) A slow journey down the tube, which might add several days to anovum apparently eighteen or nineteen days old. So that if insemination andovulation coincided and fertilization took place forthwith, the ovum may bethe maximum age, viz. twenty-five or twenty-six days. In this connection itmay be pointed out that Grosser estimates the tube journey to be fourteendays at least under normal conditions, and at other times perhaps twenty days.

Between a probable minimum age of eighteen or nineteen days and a maxi-mum age of twenty-five or twenty-six days is a period of seven days-aninterval of uncertainty. For the present, therefore, we must assign the ovumto the end of the third or to the early part of the fourth week of development.

GENERAL DESCRIPTION OF THE OVUM

The specimen lay in 10 per cent. formol for two days, and was then trans-ferred to 60 per cent. alcohol, then 70 per cent. and then 80 per cent., when itseemed to be in>a satisfactory condition for examination.

The ovumiwas enclosed in an envelope of decidua on which no scar couldbe detected. In shape it was rounded, flattened and lenticular (not unlike anordinary tabloid, but not quite so flattened), and it measured 13 x 11 x 8 mm.On dissecting away the outer capsule of decidua, which separated quite easily,the chorionic vesicle with well-marked villi was exposed. When completelyseparated the vesicle measured 10 x 7-5 x 4 mm., so that the decidual capsulewas from 1-5 to 2 mm. in thickness. On opening the vesicle, which was filledwith a light-greyish mucin-like substance-the magma reticulare a verysmall elongated papilla, attached by one extremity only, was found, the restof the papilla projecting into the cavity of the ovum and connected by strandsto the magma. The projection measured in spirit and before imbedding inparaffin about 2 mm. in length and about 1 mm. in breadth at its widest part.It must be pointed out that these measurements are probably too great, sinceone dare not touch the specimen with the dividers in case it should suffersome damage. Much time was spent in trying to obtain a photograph withoutany satisfactory result, and finally a freehand drawing was made with theassistance of the stereoscopic dissecting microscope at a magnification of15 diameters (fig. 1). By these means the amnion, yolk-sac and body-stalkwere brought clearly into view, together with the prominent caudal projectionof the embryo-anlage, all these points being fully confirmed by subsequentexamination of the serial sections. The drawing shows in addition the charac-teristic elevations or knobs on the yolk-sac, representing the angioblast, somevilli (which measured 1 to 1-5 mm. in length) projecting from the outer surfaceof the chorion, and some maternal blood, also on the outer surface of thechorion and visible through the thin chorionic layer.

The projection with a small piece of the chorion to which it was attachedwas stained in bulk, borax-carmine being used. It was cut by Professor Carlier,

6


to whom I am much indebted for the trouble he has taken to obtain a goodseries of sections. Though not coming up to ideal requirements (some of thesections are broken owing to somewhat imperfect preservation), I was ableto make a reconstruction in wax which turned out to be exceedingly usefulas a means of interpreting certain obscure grooves on the embryo-anlage,and for settling beyond doubt the line of the axial structures. The bulk of

w'-

T....._.-

Fig. 1. The "Embryonic Papilla" attached by the body-stalk to the chorion. From a freehanddrawing by Mrs P. Thompson. x about 40.

the sections are quite satisfactory for study, and this is indeed fortunate,seeing that the combination of circumstances, which brings such a rare speci-men, with a really good history, into the hands of an investigator, occurs soseldom. Altogether, reckoning from the cranial end of the embryonic shieldto the blind end of the allantois, there are eighty-five sections. As the sectionswere each 10 microns thick, this gives a length of the shield plus allantois of*85 mm. From the cranial end of the yolk-sac to the attachment of the body-stalk to the chorion , the length estimated for the number of sections is -1 2 mm.

THE EMBRYO AND ADNEXA

The embryonic vesicle is similar in general form to that of Graf Spee'swell-known Glaevecke ovum: the main features are shown in the drawing infig. 1 already described and in the diagrammatic figs. 2 and 3. The embryonicshield, though it is a good deal broader in proportion to its length, more nearlyresembles that of the Frassi ovum; but there is no neurenteric canal and theirregular ridges which are present do not appear to bound a neural groove.

7

8 Peter Thompson and James C. Brash

There is a well-defined caudal projection or tail-fold and a less well-definedhead-fold. The shield is *68 mm. in length measured from the cranial reflectionof the amnion to the caudal projection, and the estimated length includingthe caudal fold is nearly *9 mm. The greatest breadth, which is found a littlein front of the middle of the shield, is also about *9 mm. In association withthe ill-defined head-fold there is apparent evidence of the commencing forma-

Fig. 2. Diagrammatic reconstruction of the embryonic shield, etc., to show the relation of theprimitive streak, the median elevation and the two lateral grooves. The position of the head-process is indicated by a stippled band extending forward from the cranial end of the primitivestreak beneath the median elevation. The relation of the amnion and the allantois to thebody-stalk is also indicated. Drawn to scale, x about 80.

tion of a foreguit, cut separately from the yolk-sac in five sections; but, as thereis in this region some distortion of the vesicle with collapse and infolding ofthe amnion and yolk-sac, it remains doubtful whether the foregut appear-ance is to be attributed to these causes.

The irregular ridges which -are present on the shield, somewhat similar tothe ridges on the shield of the embryo about the same stage of development


described by Ingalls, have provided rather a difficult problem; their relationto the axis of the embryo is not at first sight obvious. It was to elucidate thispoint that Professor Thomson made the reconstruction to which he refers. Iknow that he did not look upon the resulting model as completely satisfactory,and there is no doubt that it cannot be taken as an exact representation of theoriginal. This is due to the absence of guide lines, a serious handicap when itis realised that the sections are oblique to both the median plane and to thesurface of the shield; in addition there is evident distortion of a number ofthe sections. The model itself is unfinished, and as it was never intended to

Fig. 3. Diagrammatic median sagittal section; the head-process, etc., as in fig. 2. Drawn toscale, x about 80.

be more than an incidental help in interpretation of the appearances of thesections and an aid in settling the question of the middle line, I do not feeljustified in reproducing it. I prefer to use it, as was Professor Thompson'sintention, along with a close study of the sections themselves, in order toreconstruct diagrammatic representations of the surface of the shield and ofan ideal median sagittal section of the ovum.

THE SURFACE OF THE SHIELD

The reconstruction of the surface of the shield is given in fig. 2, which isdrawn carefully to scale. In general shape the dorsal aspect of the shield is

9


oval with its long axis transverse to the long axis of the embryo. The cranialend of the shield is represented by one side of the oval and is bent slightlydownwards: the caudal end of the shield appears as a narrowing prolongationof the other side of the oval; it is markedly bent downwards and the projectionthus formed is indented in the middle line by the primitive groove. The groovebecomes shallower as it is traced forwards to end, a little less than one-thirdof the distance from the caudal projection to the cranial end of the shield, atthe point where the median elevation and the right depression next to bedescribed commence. The whole length of the primitive groove is estimatedto be *38 mm.

Immediately in front of the anterior end of the groove there commencesa median elevation of the shield in the position usually assigned to Hensen'sknot. This elevation, accentuated by the obliquity of the sections and inaddition rendered very prominent by the presence on each side of a depressionor groove, extends forwards on the shield for a distance a little greater thanthat occupied by the primitive groove, and reaches therefore about the junctionof the anterior and middle thirds of the shield. On each side of the medianelevation is a groove, narrow behind but broadening in front; these groovesare about the same length. The left commences at the middle of the medianelevation, extends forwards and to the left and fades away in the cranial halfof the shield without quite reaching its edge. The right begins at the hinderend of the median ridge, where it forms a deep depression immediately to theright of the anterior end of the primitive groove, and extends to the lateraledge of the shield about its middle. The interpretation of these ridges dependsupon a study of the axial structures in section.

THE AXIAL STRUCTURES

Fig. 4 is from a section a little in front of the middle of the cranial half ofthe shield. It demonstrates the general structure of the shield and shows thatthe ectoderm and the entoderm are in this region separated by a small amountof (primary?) mesoderm. There is here no indication of a neural groove. Thesections in this region are believed to be practically vertical to the surface ofthe shield, as is evidenced by the single layer of nuclei in the entoderm and theamniotic ectoderm. The embryonic ectoderm, on the other hand, shows astratification of its nuclei, two and in some places three deep, and, as the three-layered nuclei are mostly confined to an area on each side of the middle line,it is possible that we see here the commencing formation of the neural plate.Close to the entoderm in the middle line are to be seen a few mesoderm-likecells in the position where the head-process is situated further back. Thesecells, however, do not constitute a forward continuation of the head-processas the same region of the entoderm is a continuous single layer both in frontof and behind this particular section. It is to be noted that there is in fact noevidence in the cranial part of the shield of a "completion plate" continuing


the line of the head-process forward. We pass now to the caudal end of theshield.

Fig. 5 is taken from a section a little in front of the middle of that part ofthe primitive streak which appears on the dorsal aspect of the shield, i.e. infront of the caudal bend. Here is to be observed the continuity of the three

Fig. 5. Transverse section of the primitive streak region in front of the caudal bend; descriptionin the text. x 385.

layers, but there is by no means complete fusion. The entoderm is somewhatdamaged on the left, but it passes as a continuous thin layer from side to sideclosely united to, though quite distinct from, the mesoderm. The ectoderm,which is relatively independent, is thickened in the middle line where thenuclei are three and four deep; here also are to be observed the primitivegroove indenting the surface, and, corresponding to this, a ridge-like depressionof the ectoderm towards the entoderm. It is from the anterior end of this

11

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ridge that the head-process appears to take origin. Behind the region of thissection the streak becomes progressively thinner until, when a point a littlebeyond the caudal bend is reached, it becomes reduced to a single layer ofentoderm and ectoderm in apposition in the region of a cloacal membrane.The position of the cloacal membrane is indicated in fig. 3, but, owing to thegreat obliquity of the sections to the surface in this region, it is hardly possibleto determine its exact extent. We now turn to the head-process itself and therelation which it presents to the anterior end of the primitive streak.

Now about the point where the primitive groove, as seen in fig. 5, givesplace to the median ridge already mentioned and seen in the next sectionfigured, i.e. in the position assigned to Hensen's knot, there is the appearanceof a downgrowth of a wedge of cells from the ectoderm in direct continuitywith the ridge beneath the primitive groove. This apparent downgrowth isclearly marked four or five sections behind the most anterior showing theprimitive groove, and is the result of the sectioning of a column of cells whichis found to continue the line of the primitive streak forwards between theectoderm and the entoderm. Its centre appears at first to be slightly to theleft of the anterior end of the primitive streak, but as it passes forward it liesdirectly beneath the median ridge of the shield. It is in continuity behind withthe ectoderm at the anterior end of the streak as stated, and it maintains thesame relation to the mesoderm as is exhibited by the primitive streak itself.Traced forward it begins at once to separate from the ectoderm and is fromits origin in contact with the entoderm; in the course of eight or nine sectionsit is entirely free from the former and closely united to the latter.

A section at the most favourable point (figs. 6 and 7) makes clear the generalrelations of the column, which is thus identified as a head-process. The figuresalso show that although there is no distinct lumen present yet the dorsal cellsare arranged fanwise as if the lumen were about to appear. The section figuredis situated fifteen sections in front of the origin of the process from the ecto-derm of the knot and fourteen sections behind its cranial termination: thewhole length of the head-process is estimated to be nearly *3 mm. In front ofthe process the simple condition of the entoderm, as seen in fig. 4, appears atonce, and, as already stated, there is no evidence of the formation of a "com-pletion plate" continuing the line of the process forward. The thickening ofthe process is merely replaced by (primary?) mesoderm and the entoderm isunaffected. These topographical points are summed up in the shield diagramof fig. 2 and the schematic sagittal section of fig. 3, where the head-process isrepresented by a stippled band passing forward beneath the median elevationof the ectoderm and in continuity with the entoderm. There can be little doubt,judging from the absence of a definite canal and the manner in which the pro-cess ends in front, that we are dealing with an example of the head-process incourse of formation, probably just before the appearance of a lumen and thebreaking down of the ventral floor. There is no sign of perforation towardseither the ectoderm or the entoderm, so that the stage is without doubt previous

Head-Proce8s and Commencing Archenteric Canal 13

to that of the notochordal or archenteric canal and afortiori of the neurentericcanal.

The more highly magnified view of fig. 7 shows very clearly the arrange-

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Fig. 6. Transverse section at the midpoint of the head-process showing the ridges and grooves onthe shield and the relation of the head-process to the median elevation. x 95.

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Fig. 7. Portion of the preceding, x 300, showing the head-process in detail.

ment of the cells. The distinction between the ventral simple layer (plaquelecithoenterique of van Beneden) and the dorsal clump with its radial arrange-ment foreshadowing the canal (plaque notochordale of van Beneden) is indi-


cated both by the actual arrangement of the cells and by the staining reactions.These figures (6 and 7) also demonstrate that the line of the head-processcorresponds to the line of the central elevation of the shield and that this isto be considered as indicating the axial line of the embryo. The appearance ofthickening of the ectoderm along this ridge is probably largely due to theobliquity of the sections, which is also the case with the other two ridges

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Fig. 8. The wall of the yolk-sac, near the cranial pole, showing blood-island. x 385.

previously mentioned. All three ridges must be considered to be due to a

folding of the surface of the shield, partly due to exuberant growth and partlyartificial.

THE AMNION

The amniotic ectoderm consists of a single layer of flattened cells con-

tinuous with the peripheral two-celled embryonic ectoderm and backed byan equally thin mesodermic covering. The amniotic cavity is a good dealdistorted in many of the sections, but there is no doubt that there is a greaterdepth of this space at the cranial than at the caudal end of the shield. Inthe region of the caudal bend the amnion appears to be stretched over theshield, and as this diminution of the cavity corresponds with the presence ofthe grooves on the shield, the impression that these grooves may be due to

... .7

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14


an exuberant growth of the shield is somewhat strengthened. Traced back-wards the amnion is found to bend in conformity with the caudal bend of theshield itself, and, with a slight convexity towards the deep depression betweenthe shield and the body-stalk, it passes directly on to the dorsal aspect of thelatter. It covers the stalk for about half its extent, and, as a result of the bendmentioned, the last few sections of the amnion appear as a narrow space lyingon the left side of its dorsal aspect (figs. 3 and 10). There is no evidence of thepresence of an amniotic duct, the amniotic ectoderm remaining histologicallythe same at the extremity of this small diverticulum as elsewhere, with noextension towards the chorion.

THE ENTODERMIC CAVITY

The median sagittal diagram of fig. 3 indicates clearly the conditionspresent. In five sections at the cranial end the lumen of the intraembryonicportion is cut separately from the yolk-sac cavity, but a doubt, accentuatedby the obliquity of the sections, remains whether this is in reality foregut ordue to a distortion of the wall of the yolk-sac. There appears, however, to besome thickening of the mesoderm, with. a doubtful coelomic rudiment, in theangle between. The allantoic diverticulum extends from the dorsal part of thecaudal wall of the yolk-sac into the body-stalk, which it traverses for rathermore than half its length. The total length of the allantois is estimated to be*14 mm. There is no hindgut.

THE MESODERM

A thin layer of (primary?) mesoderm-mostly one cell thick--extendsthroughout the shield, while secondary mesoderm is in process of active forma-tion in the primitive streak and is in continuity with the head-process in front,with the somatopleuric and splanchnopleuric layers, and with the chorionicmesoderm along the body-stalk. The chorionic mesoderm forms a continuouslayer lining the chorionic ectoderm and extending into the primary villi.

ANGIOGENESIS

The distribution of the angioblastic tissue is, with doubtful exceptions inthe body-stalk, confined to the wall of the yolk-sac. The evident blood-islandsin this situation have already been noted in the general description of the ovum,and a detailed examination of the sections reveals that they are distributedthickly on the whole of the ventral aspect of the sac and extend on to bothits cranial and caudal extremities. On the whole it appears that the islandsin the cranial half of the sac are in a more advanced state of development. Itis not proposed to give a detailed histological description of the appearancespresented by these blood-islands, but attention may be directed to certainimportant features which are to be seen in the illustrations given.

It will be observed from fig. 4 that the entoderm for about the dorsal halfof the wall of the yolk-sac consists of a single layer of cells, whereas in the

15


ventral half it is thickened so that there are two, three and in some placesfour and even five nuclei. It may be thought that this appearance isdue to distortion and consequent obliquity of the sections, but a carefulexamination of all the sections reveals that this is the condition throughoutthe extent of the yolk-sac. Associated with this difference it is found that,whereas in the dorsal half of the yolk-sac the overlying mesoderm is separatedfrom the entoderm by a distinct space and is clearly independent of it, in theventral area there is no such clear separation between the two. Here also themesoderm is thickened and the blood-islands occur. The separation of the yolk-sac into two areas, a dorsal and a ventral characterised by the differences inthe entoderm mentioned, was described by Minot, and in Streeter's account ofa human embryo (Mateer) of the presomite period the same separation of themesoderm from the entoderm in the dorsal half of the sac is noted. In thatembryo, however, which, in a younger stage than the present specimen,exhibits a much less differentiated condition of the yolk-sac blood-anlage, itis the ventral part of the mesoderm which is thinner and "fused tightly withthe entoderm." The significance of these observations must lie in their relationto the formation of the blood vessels and the blood cells.

If we now examine the blood islands themselves we find that there are allintermediate stages present between the extremes of small clumps of cellslying between apparently simple entodermic and mesodermic layers and com-pletely formed vessels with uninterrupted endothelial walls containing thedeveloping blood cells. The three main stages are illustrated in fig. 4, wherefrom left to right are to be seen (1) clumps of cells between entoderm andmesoderm each single-layered, (2) partially formed vessels with endothelialwall unformed towards the thickened entoderm, and (3) a fully formed vessel.The middle of these stages is illustrated on a larger scale in fig. 8, taken froma different section nearer the cranial pole of the yolk-sac. This section showsthe-formation of the endothelial wall on the side of the island away from theentoderm and the characteristic relation of the blood cells to the entoderm,from which they appear to hang in a cluster into the lumen of the developingvessel. In fig. 9, on a still larger scale, is shown the portion of the entodermwith which these cells are apparently continuous. It will be observed from thisfigure that the cells from which the clump in the lumen apparently springs aredifferentiated from the cells next the cavity of the sac by a number of points.There is the same absence of cell outlines throughout, but the cytoplasm sur-rounding the nuclei in the deeper layer is more clearly differentiated, the out-lines of the nuclei are less regular, the nuclei are more deeply stained, and thelayer as a whole is separated from that next the cavity by a row of spaces.It is clear that these cells are to be separated from the overlying entoderm,and that between the two layers will be formed the completion of the endo-thelial wall. Although the appearances here described are at first sight sug-gestive of the origin of the blood cells from the entoderm, yet there is nounequivocal evidence to warrant a conclusion on this difficult question.

16

Head-Proce8s and Commencing Archenteric Canal

It should be noted that there are great variations in the distribution of thevessels in embryos about this stage of development. The contrast, for example,between this ovum and Streeter's Mateer specimen is very marked. In thelatter, blood vessels are present in all parts of the chorion and in many of the

7nM

Fig. 9. Portion of the preceding (the left upper corner of the island) to show the arrangement ofthe cells on the yolk-sac side of the island. x 1750.

villi, while the differentiation of the vessels on the yolk-sac is restricted tothe caudo-ventral half and has not advanced so far as in the Whitehousespecimen.

THE COELOM

There is no indication of an intraembryonic coelom with the exception ofa doubtful space in the mesoderm between the cranial wall of the yolk-sacand the doubtful foregut. Elsewhere the intraembryonic mesoderm is almostentirely one cell thick. There is no special remark to make regarding the exo-coelom, beyond calling attention to the statement in the general descriptionthat there was a considerable quantity of magma present, to which theembryonic papilla was connected by strands.

Anatomy LVTII

17

2


THE BODY-STALK

The structure of the body-stalk is illustrated in fig. 10, in which is to beseen the allantois in the centre of the lower part of the stalk and, on the side,

a...;l-- - q

Fig. 10. Section of the chorion and the body-stalk, showing the allantois in the centre and theamniotic diverticulum on the side of the stalk. x 95.

a section of the amniotic diverticulum which passes along the stalk for a shortdistance. It will be noted that the mesoderm immediately surrounding theallantois is more compact than that which is connected with the chorion.

THE CHORION AND VILLI

Figs. 11 and 12 are added, without detailed comment, to demonstrate thestructure of the chorionic wall and the villi. It may be noted that the dis-tribution of the villi is very irregular, that the cyto- and plasmodi-trophoblastlayers are everywhere very distinct, and that the cores of the villi consistexclusively of undifferentiated mesoblast, in most cases shrunken away fromthe walls in preparation. There is no sign anywhere of vascularisation.

SUMMARY

1. There is an excellent clinical history, by means of which the age of theovum can be placed between a minimum of eighteen or nineteen and a maxi-mum of twenty-five or twenty-six days.

2. The head-process is in course of formation, and the stage of develop-ment is probably just before the appearance of the archenteric canal and thebreaking down of the lecithoenteric plate.

3. The amnion is stretched over the caudal end of the shield and is con-

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Fig. 11. Chorion and villi. x 142.

Fig. 12. Portion of the preceding. x 350.

2-2

19

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. .,. f'' ";l,,, ,,.

l-. I-i.-, -( "

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Peter Thompson and James C. Brashtinued as a short diverticulum on the dorsal and left side of the body-stalk.There is no evidence of an amniotic duct.

4. There is a doubtful foregut, no hindgut, and an allantoic diverticulumof the yolk-sac extending about half-way along the stalk.

5. Blood and blood vessel formation is restricted to the ventral wall ofthe yolk-sac and is slightly more advanced towards the cranial end.

6. There is no intraembryonic coelom.

In conclusion I have to thank Mrs Thompson for her ready assent to theproposal that the work begun by her late husband should be completed, -andfor her kindness in placing at my disposal his unfinished MS. and notes. AlsoI have to acknowledge my indebtedness to Professor Barclay-Smith for hisadvice and to Professor Arthur Robinson for his kindness in looking over thematerial at my disposal and fA helpful suggestions.

REFERENCES

(1) VAN BENEDEN. "Sur la presence chez l'homme d'un canal archent6rique." Anat. Anzeig.xv. 349-356, 1899.

(2) BRYCE and TEACHERL Contrtbutton to the 8tudy of the early development and imbedding of thehuman ovum. Glasgow, 1908.

(3) FRXNAEL. "Das zeitliche Verhalten von Ovulation und Menstruation." Zentralbl. f. G~yndkol.No. 46, p. 1591. 1911.

(4) FaRssi. "Ueber ein junges menschliches Ei in situ." Archiv f. milr. Anat. u. Entwick.ILxx. 492-5O5. 1907.

(5) GROSSER. "Ein menschlicher Embryo mit Chordakanal." Anat. Hefte, xLvn. 649-686.1913.

(6) - "Altersbestimmung junger menschlichen Embryonen; Ovulations- und Menstru-ationstermin." Anat. Anzeig. XLVia. 264-283. 1914.

(7) INGALLS. "A human embryo before the appearance of the myotomes." Contributions toEmbryology, No. 23, Carnegie Inst. of Wash., Pub. No. 227, pp. 111-134. 1918.

(8) MINOT. " The origin of the Angioblast and the development of the Blood." Keibel and Mall'sManual of Human Embryology, vol. I. 1912.

(9) STRARL. "Ueber einen jungen menschlichen Embryo, nebst Bemerkungen zu C. Rabl'sGastrulationstheorie." Anat. Hefte, Liv. 115-146. 1916.

(10) STREETER. "A Human Embryo (Mateer) of the Presomite Period." Contributions to Embry-ology, No. 43, Carnegie Inst. of Wash., Pub. No. 272, pp. 389-424.

(11) TREPEL. "Altersbestimmung bei menschlichen Embryonen." Anat. Anzeig. xLvi. 385-398.1914.

(12) WILSON and Hui. "1 Observations on the Development of Ornithorhynchus." Phil. Tran8.,B, vol. 199, p. 61. 1908.

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a human embryo with head-process and commencing archenteric

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