here and there large and granular with round nuclei, but the whole of the epiblastic layer is now composed of thickened cells, almost columnar with rounded nuclei, and for a given length there are many more nuclei than there were at that region during the sixth and seventh days. In fig. 9 a piece of the same region a few hours later is shown, and here the epiblast is seen to be so thickened as to be actually several cells thick, in fact, a proliferation of cells is taking place outwards.

Figs. 10 and 11 are still later stages of the same area.

I believe that to understand the first outgrowth of these papillæ, both the small ones scattered over the lower pole, and the area nearer to the embryonic disc, the great change that the embryo has now undergone in the physical and mechanical conditions must be taken into careful consideration.

During the fifth, sixth, and seventh days I described in my previous paper the growth of the walls of the vesicle as being due to the hydrostatic pressure within it, together with the multiplication of the cells of the walls of the vesicle, support being rendered to the delicate wall of the vesicle by the albumen layer. The cells of the wall (the epiblast) are very much flattened because of the tension produced by the hydrostatic pressure.

The hydrostatic pressure is sufficient to keep the cells always taut, and any increase in size of a cell owing to growth, or any aggregation of cells by multiplication, is prevented by their being flattened out by the internal pressure as soon as formed. Thus all the cells are uniform in thickness, and extra activity of one part shows itself by extra expansion of that arc of the vesicle.

What happens, however, when the walls of the uterus, by reason of the great size now attained by the blastodermic vesicle, affords supports to the walls which was hitherto wanting? It must decrease the ratio of hydrostatic pressure to the rate of growth of the cell wall.

If the amount that the cells are stretched is constant when the hydrostatic pressure is to the rate of growth of the cell VOL. 37, PART 2.-NEW SER.

M

walls as, say, 10 is to 10, then when the hydrostatic pressure (P) is to the rate of growth (R) of the cell walls as say 8:10, it follows that the cells will not be so much stretched as when PR 10: 10.

The actual pressure within the vesicle no doubt does not diminish, more probably it increases, but the relation of P: R is altered by the fact that additional resistance is now added without by the walls of the uterus. At any rate, it upsets the ratio formerly existing.

The result, I believe, is that now the rate of growth of the cells of the wall is as compared with the rate of increase in size of the blastodermic vesicle greater than it was before, so that when a cell "grows" and "divides " it no longer becomes at once stretched out, but forms a rounded granular cell, or group of cells, as in figs. 5 and 6. The cells which are for the time inactive will remain flattened, for elasticity is not an attribute of protoplasm.

This is the case at the lower pole of the blastodermic vesicle and at the lower sides. In the region near the embryonic disc (where it has all along been assumed that there is a more active growth) it is found that almost every cell has evinced signs of activity, for here the whole area has become thickened, and the cells far more closely packed than they were, and almost columnar instead of being flattened (fig. 8).

It is, I believe, usual to describe the first attachment as occurring between the ectoplacenta of the embryo and the placental lobe of the uterus. This I am convinced is not an accurate statement. The first actual attachment is between the lower parts of the blastodermic vesicle and the periplacental and obplacental folds.

The exact course of the procedure I am doubtful about, but I believe it to be a combination of at least two main causes, but it may involve more; or possibly it is wholly due to only one of the two I am about to mention.

The first attachment is effected by means of the "papillæ," or thickened spots of epiblast of the lower pole of the embryo already described (figs. 5 and 6, a., b., c.). In fig. 7 one of

these thickened spots is shown to be on the point of effecting an attachment. It may be noticed to be wedge-shaped in section; it is a little blunt cone. Practically each papilla assumes this shape, and is being pressed against the epithelium lining the uterus. In this figure (and almost any number might be drawn showing the same characters) the papilla certainly looks as though it were piercing the epithelium by reason of the pressure from within the vesicle.

Of course the actual hydrostatic pressure will be the same at a. as it is at e., but nevertheless a greater pressure will be exerted on the uterine wall at the apices of any knobs on the wall of the vesicle than at the area between them if the uterine wall is in a state of tension, which undoubtedly it is at this time.

If we consider that in all probability the uterine epithelium is a softer material than the muscular and connective tissue outside it, it is all the more probable that the softer (if it is softer) uterine epithelium will give way between the two.

I think it quite possible that this may be the only necessary cause, and by this means the "papilla" reaches the capillary system of blood-vessels in the uterine connective tissue, a point of the utmost importance to the welfare of the embryo.

On the other hand, although I have no doubt that the additional pressure which exists at the points of these knobs is of much importance in that it causes very close contact between the uterine epithelium and parts of the wall of the blastodermic vesicle, yet it is more than possible that the breaking down of the uterine epithelium at those points is not due to mechanical pressure alone, but to a chemical or a physiological process, such as absorption of the uterine cells by the vital activity of the cells of the knobs. But the possibility should not, I think, be lost sight of that the first breaking through of the uterine epithelium at these points may be entirely due to mechanical pressure alone.

A point to which special attention must here be drawn is

that the moment after the uterine wall comes to take the place of the albumen layer as a support, then the greater part of the expansion of the combined vesicles must be that part furthest removed from the embryo, because it is here that the uterus wall is infinitely less resistent, and with it will go that part of the vesicle to which it is attached.

On the Importance of the Albumen Layer and Zona radiata.

Those who have followed my account of the development of the blastodermic vesicle of rabbit between the eightieth hour and the time of attachment of the vesicle to the walls of the uterus at about the 170th hour, must have seen how important a part the albumen layer plays in producing the form actually assumed by the vesicle. I pointed out how that the thin cellular wall of the blastodermic vesicle would be itself quite able to withstand the hydrostatic pressure within; and, further, that it is not until the vesicle has attained such a size as to stretch the walls of the uterus as to cause them to afford the support necessary to prevent the bursting of the vesicle, that the albumen layer was lost. By this time the albumen layer has become exceedingly thin, and the disappearance of it is brought about by its rupture. Traces of it may be found curled up and crumpled several days later. Once burst, its function, as far as I can judge, is at an end.

Now it has almost certainly at least one other very important influence upon the development of the rabbit. By its presence until the eighth day it absolutely prevents the cellular tissue of the blastodermic vesicle from coming into close contact with the cellular tissue of the uterus. The embryo up to the eighth day is as free probably from the protoplasmic influence of the mother, as is the egg of a bird after it has been covered with a thick calcareous shell. There is also, it will be remembered, another coat to the ovum, the zona radiata, which is present from the very first, and has a similar effect to that which the albumen layer has, but being less thick its effect is more evanescent. The two coats may be considered as one.

As regards the rabbit. I have shown in considerable detail how many events are, or at least may be, explained by external influences (such as albumen layer, hydrostatic pressure, pressure of uterus, rupture of albumen layer) acting in conjunction with a simple steady force or energy, the primary centre of cell multiplication.

In doing so, it will be remembered that in connection with the actual forms assumed, and phases passed through, in the rabbit, the presence of the albumen layer, the size of the cavity of the uterus, and even the shape of the walls of the uterus, had important consequences ascribed to them.

If my line of argument has been correct, the effects produced by the albumen layer and the size and shape of the uterus must be very different or absent altogether in forms in which these conditions are different or absent. As regards the size of the ovum itself, there is very little difference amongst mammals.

Let us examine the case of a rat,-a rodent, and so not very distantly removed genetically from a rabbit. And yet how different is the form assumed in the earliest stages of development! Do the conditions differ from those in the rabbit, and if so, how?

They differ in these respects:

(i) There is no zona radiata or albumen layer.

(ii) The diameter of the uterus is very much smaller, and the lumen proportionately smaller still.

(iii) The walls of the uterus are of a more uniform thickness. In the rabbit the zona radiata is so quickly covered by the albumen layer that it cannot be said to have in itself much effect as a support or protective coat.

In the rat there is no zona radiata or albumen layer. The ovum develops freely in the cavity of the uterus unprotected by any coat. It would seem to pass very rapidly down the Fallopian tube. Robinson found one early stage of segmentation; from this he figures the mesial section, which shows parts only of twelve segments, so we may conclude that his specimen was a fairly early stage of segmentation-comparable, perhaps, to that of the rabbit of the forty-eighth hour.