"heat," which in the absence of coitus is generally very prolonged, there

Transcription

1 CYCLICAL CHANGES IN THE VAGINA AND VULVA OF THE FERRET. By F. H. A. MARSHALL. From the Institute of Animal Nutrition, School of Agriculture, Cambridge. (With six figures in three plates.) THE changes that take place in the ovaries and uterus of the ferret during the normal cestrous cycle formed the subject of an investigation, the results of which were published some twenty-eight years ago (MARSHALL, 1904). It was then recorded that during the period of "heat," which in the absence of coitus is generally very prolonged, there is a pronounced swelling of the vulva. More recently in the course of researches carried out in conjunction with Mr HAMMOND on cestrus and pseudo-pregnancy (1932), exact records were obtained of the changes in the size of the vulva at different stages in the cycle. It was shown that the vulva enlarges to about fifty times its ancestrous size at the beginning of heat and persists at that size until the cessation of heat. The changes, as measured at regular intervals, afforded an index of the animals' condition. During pregnancy, pseudo-pregnancy, and lactation the vulva was found to be at its minimal size, just as it is at the ancestrum before heat has commenced. The swelling of the vulva, therefore, was characteristic of the "follicular stage" of the cycle, coming to an end at or shortly after ovulation, while the absence of such swelling is the normal condition during the "luteal stage," as well as during the ancestrum. It is interesting to note that these changes have their exact parallel in the cyclical swelling and shrinking of the sexual skin of the baboon and other Primates as described by ZuCKERMAN and PARKES (1931, 1932), who have shown that they have a definite relation to the maturation and rupture of the Graafian follicles and the formation of the corpora lutea. In the paper by HAMMOND and MARSHALL (1932) no account is given of the vaginal cycle in the ferret or of the histology of the vulva at different phases. Owing, however, to the kindness of Mr HAMMOND I have been able to make use of the material obtained at the time of the former inquiry, and I take this opportunity of thanking Mr HAMMOND for the help he has afforded in this matter. That the swelling of the vulva in the ferret and that of the sexual skin in the monkey are due to cestrin has been shown by PARKES and ZUCKERMAN (1931), who have induced both these processes in oophorectomised animals as a result of injecting cestrin.

2 132 Marshall The walls of the vagina in the ferret are histologically of the same general type as those of the dog (EV-ANS and COLE, 1931) and other Mammalia. There is a more or less stratified epithelium which undergoes definite cyclical changes, and a submucous layer below consisting of a somewhat fibrous connective tissue and containing nodules of lymphoid cells. It is of the latter tissue that the vulva is composed. At the anterior end of the vagina some fibro-cartilage is present in the connective tissue. This is probably the homologue of the os penis of the male ferret. The changes that occur during the successive stages of the cycle may now be described: (1) Ancestrum (Ferret No. 4 in HAMMOND'S and MARSHALL'S paper). Killed just before the commencement of the breeding season. The epithelium is columnar in type, and consists of four or five layers of rather shallow cells. Some cornification is beginning. The connective tissue is compact, the nuclei being fairly close to one another. (2) Ancestrum (Ferret No. 9, H. and M.). Killed after the close of the breeding season. The epithelium is thin and consists of two or three layers of low columnar cells arranged rather irregularly. There is no cornified layer. In general appearance there is a resemblance to the vaginal mucosa of the bitch as described by EVANs and COLE, as well as to that of the baboon during lactation as described by ZUCKER- MAN and PARKES (1932). The submucous connective tissue is compact. (3) Pro-cestrum or early oestrus (Ferret No. 20, H. and M.). The epithelium is several layers deep, and in the deeper part is high and squamous. There is a well-marked cornified layer. The vulval swelling has begun, the nuclei in the connective tissue being separated by a considerable distance. (4) Pro-cestrum or oestrus (Ferret No. 3, H. and M.). The stratified epithelium is high and squamous, the innermost layer being columnar. The cornified layer is similar to No. 3, above. The submucous connective tissue is very spongy in appearance, with many elastic fibres (figs. 1 and 1A). (5) CEstrus (Ferret No. 1, H. and M.). This ferret had been on heat a long time. The histological appearance is similar to No. 4 above, but sloughing of the cornified layer had begun. The nuclei in the submucous layer are very widely separated. (6) Pseudo-pregnancy (Ferret No. 10, H. and M.). This ferret had been pseudo-pregnant for two weeks, having copulated with a vasectomised male. The ovaries contained corpora lutea. The vaginal epithelium was still stratified, the cells being mostly of the high columnar type, especially on the inside. The cornified layer was mostly shed, but some cornified cells remain; there is a rough outer edge. The submucous connective tissue still appears somewhat spongy (figs. 2 and 2A).

3 Cyclical Changes in Vagina of Ferret (7) Pseudo-pregnancy (Ferret No. 6, H. and M.). This ferret had been pseudo-pregnant six weeks. The ovaries contained old corpora lutea. The vaginal epithelium is formed partly of high columnar cells, but on the outside the cells are swollen, the nuclei being elongated. There is no cornified layer. The submucous connective tissue contains elongated spaces and many small vessels. Some lymphoid degeneration is apparent and in places there are quantities of lymphocytes. (8) Pro-cestrum or cestrus (Ferret No. 12, H. and M.). This ferret was killed eight weeks after the commencement of pseudo-pregnancy, and therefore eight weeks after the close of the previous cestrus. The vaginal epithelium consists of several stratified layers, with a row of columnar cells on the inside next to the connective tissue. A thin cornified layer is also present. The submucous connective tissue is fairly compact and uniform, the cell nuclei being not far apart. Remains of lymphoid nodules could be seen with lymphocytes along the lines of spaces in the tissues. (9) Pregnancy (Ferret No. 17, H. and M.). This ferret had been pregnant three weeks. The vaginal epithelium is thin and small, with small irregularly arranged cells above and a single row of columnar cells below. There is no cornification. The submucous layer is somewhat spongy. (10) After parturition (Ferret No. 19, H. and M.). The ferret had given birth a few hours previously. The vaginal epithelium is stratified but thin, with an inner layer of rather low columnar cells. On the extreme outside edge are a number of leucocytes. There is no cornified layer. The connective tissue of the vulva is somewhat spongy, with a number of small capillaries. (11) Lactation (Ferret No. 14, H. and M.). The ferret had been suckling seventeen days. The vaginal epithelium is thin-only two or three cells deep (cf. No. 2, above). There is no cornified layer. The connective tissue shows some signs of a recent lymphoid invasion, but is fairly compact (figs. 3 and 3A). (12) After parturition, without lactation (Ferret No. 15, H. and M.). The ferret was beginning a new heat period. It had had its young removed immediately after parturition, sixteen days previously. There is a stratified epithelium three or four layers deep, with an inner row of columnar epithelial cells and a thin cornified layer. The submucous tissue is fairly compact, but contains some spaces. SUMMARY AND CONCLUSIONS. The vagina and vulva of the ferret undergo well-marked cyclical changes in correlation with those of the ovaries and uterus. During the ancestrum the vulva is small and the cqnnective tissue of which it is mainly composed is compact. The vagina during this 133

4 134 Marshall period is lined by a low columnar epithelium consisting of only two or three rows of cells and without a cornified layer. During the pro-cestrum and oestrus the vulva swells up to about fifty times its ancestrous size, the submucous connective tissue becoming spongy and the nuclei of the cells widely separated. The vaginal epithelium is several layers in thickness, and in the deeper part the cells become high and squamous. There is a pronounced cornified layer. Later, during cestrus, the cornified layer begins to slough, the process being continued over some time. The entire period represents the " follicular stage " of LOEB and other authors, and is presumably brought about by the action of cestrin. The vulval swelling serves the purpose of facilitating effective copulation which in the ferret is very prolonged. During pregnancy and pseudo-pregnancy (the latter condition in the ferret only occurring under experimental conditions as after copulation with a vasectomised male) the vulva is reduced to its ancestrous size. The reduction is accompanied by lymphoid degeneration and an invasion of leucocytes. The vaginal epithelium becomes reduced to a low columnar or cubical structure. There is no cornified layer, this being completely shed during cestrus. This period clearly represents the "luteal phase" in the ovarian cycle. It is to be noted that the vulval swelling and other characteristics of the follicular stage terminate with ovulation just as does the swelling of the sexual skin in the Primate, as described by ZUCKERMAN and PARKES. The description of the changes here recorded are in general agreement with the observations by PARKES (1930) on the vaginal smear at different stages of the cycle in the ferret. The vaginal cycle in the ferret is in a general way similar to that of the dog, as described by EVANS and COLE. It may be again remarked, however, that pseudo-pregnancy only occurs under experimental conditions in the ferret, yet under the influence of pro-gestin secreted by the corpus luteum the vagina and vulva undergo similar changes during both pregnancy and pseudo-pregnancy. DESCRIPTION OF FIGURES. The sections are of the vagina at different stages. FIG. 1. testrus ( x ca. 110). No. 4 (H. and M., No. 3). FIG. IA. CEstrus ( x ca. 430). FIG. 2. Pseudo-pregnancy (2 weeks; x ca. 110). No. 6 (H. and M., No. 10). FIG. 2A. Pseudo-pregnancy ( x ca. 430). FIG. 3. Lactation ( x ca. 110). No. 11 (H. and M., No. 14). FIG. 3A. Lactation ( x ca. 430).

5 Cyclical Changes in Vagina of Ferret 135 REFERENCES TO LITERATURE. EVANS, H. M., and H. H. COLE, " An Introduction to the Study of the (Estrous Cycle in the Dog," Mem. Univ. of California, 1931, Berkeley, California, ix. HAMMOND, J., and F. H. A. MARSHALL, Proc. Roy. Soc., B, 1930, cv LOEB, L., Amer. Journ. Anat, 1923, xxxii PARKES, A. S., Proc. Roy. Soc., B, 1930, cvii PARKES, A. S., aind S. ZUCKERMAN, Journ. Anat, 1931, lxv ZUCKERMAN, S., and A. S. PARKES, Proc. Zool. Soc., 1932, p ZUCKERMAN, S., " The Social Life of Monkeys and Apes," London, 1932.

6 Quarterly Journal of Experimental Physiology, Vol. XXIII., 1933.] [PLATE I. FIG. 1. FIG. 1A. MARSHALL, " Cyclical Changes in the Vagina and Vulva of the Ferret."

7 )uai t ly Jo fh(l m of E/,'.), ni/onallx[ l 'bysj>'i6vlo)6j IJIl. X.\II., 1!J 3,.,. [PLATE I I. I, 8, C.. I.I U q F 2. I i^ -*A 16 A 1%, % lw A., A Aw V*" I'\1(.a. MA -ni Cr.Co1,'linlI ( iti,laes il the \Vagiina ndl(v ul\va () Io Ferret."

8 S. Y t, sx * or _ $ S > f w, {/ sg ;. f,- th5> s:. t * 0 # s%, ', w; '. -_ ts- s (),C;r/clJoi/, ll'i,,/ of 1) ICa W, lu/a I'/tqi(lo9y/. Volo. X [II.. /9.1iII. r.1'4qx- N * *, f 1., W ' Aw _- X,5, I '' ' ' Yg t,... v ',,^ * fs CX r., t jo - o is.- * *i _.0y t'zr< * t * i w, f 0 _ ' _t, a ' S_S-A N41.,.+Af ftese;' f:vs! i:. e wb >\D,,, NN, Ur f F I1I 1 II (. 3. of P. t;~ 1'Fi(. 3,\..1 I LLS I IAL, ( ( 'l(id!i ( 'li Igi I It lt ¾1L1 ( nioid1 i I of, ItIe Il v 1JtJ.