VAGINAL OCCLUSION, AN ABNORMALITY I N MICE LORE MARX University Institute of General Pathology, Copenhagen TWO FIGURES In black-silver mice and two black-silver bastard strains, a curious abnormality of the genitalia sometimes occurs. A roundish hernia protrudes out of the orifice of the pelvis as shown in figure 1. Nipples and a small, non-erectile clitoris indicate the female nature of those individuals. The perineal herna can be distinguished from the scrotum by its azygos, hemispherical shape and the presence of the clitoris on its ventral surface. I n some cases there is even a more or less well-developed vaginal membrane behind the clitoris. The monstrosity becomes conspicuous from the age of puberty on. Later, the belly of these animals expands and sometimes the nipples grow as in pregnant females. The hernia may in some cases assume grotesque dimensions. At autopsy the aspect represented in figure 2 is seen. Uterus and vagina are enormously distended and through the thin walls a secretion is seen, which in younger specimens is uncolored, in older ones reddish. (According to Long and Evans reddening of the uterine fluid in normal rats occurs after copulation.) I n one mouse the content was a dark, putrid fluid. The vagina ends blindly without adhering to the skin. Its fluid-filled blind end causes the skin to bulge out like a hernia. In a female with extraordinarily distended abdomen heavy ovaries and suprarenals were found; the female weighed 20 gm. and the ovaries and suprarenals weighed after fixation and rinsing 14.4 mg. and 10.7 mg. The corpora lutea prevailed by far over the follicles. The 449 450 LORE MARX zona reticularis of the suprarenals was very broad and merged at the border of the medulla with a broad belt of fatty tissue. White mice, according to Masui ('26), retain the zona reticularis beyond the age of maturity only in the female sex; the zona reticularis becomes most prominent during the periods of ripening of the follicles. The blacksilver mice and black-silver bastards differ slightly however from Masui's albinos in that an even border between cortex and medulla with a delicate septum of connective tissue, described by Masui as a male sign, may also occur in females. But the presence of a well-developed zona reticularis together with large masses of fat on its inner border is quite unusual. In searching for the origin of the monstrosity the genetic constitution of these strains of mice should be taken into consideration. Late genital differentiation is very common among the males of these strains, so that the external genitalia during the infantile stage frequently cannot be distinguished from those of the females. The most conspicuous abnormality of the population is recessive hypophyseal dwarfism, and it would therefore be interesting to know, whether the malformation of the vagina is linked to the recessive hypophyseal defect. In fact, many of the deformed females are sisters or near relatives of the dwarfs. The known heterozygotes (viz., the mothers of the dwarfs), however, and with one exception, the dwarfs themselves, who under the influence of hypophyseal growth hormone did develop fairly well, had normal external genitalia. This one dwarf, which later showed vaginal occlusion (described as Dwarf 34 by Kemp and Marx), gave an extraordinarily strong response to a short treatment with growth hormone. In one case the abnormality was present only to a slight degree. A narrow double opening had formed, and only as the animal grew older, did the vagina occasionally protrude. This animal once bore a young one, which also possessed an abnormal constitution, supporting the view that the mon- OCCLUSION O F \'AGIh'A 451 45% IAORE MAKX strosity has an hereditary basis. The offspring of this young one, which was a male, w c n altogether normal.' The cause of lack of formatioii of a vaginal orifice ma?- lie in some hormonal disturbance or in a clcvelopmental arrest. Kietscliel ( '29) obscrvc?s that the posterior end of the vagina of the mousc is still situated at the level of the symphysis 1 week after birth. This late caudal growth makes it conceivable that the process is dependent upon the influence of an ovarian hormone. Since, however, Wiesner ( '32), clescribes normal differentiation of the female genital apparatus during the first 34 days in rats castrated at birth, such a view is unlikely. The relationship befwcben vaginal occlusion and pseudogi*aviditypresents anothei. problem. A reciprocal cffect of the genital tract on the ovary has already been ascertained. Loeb and Kouiitz ('27), and Asdell and IIammond ('33) point out the persistence of the corpora lutea after hysterectomy in guinea pigs and rabbits. Fricdnian ('29), Long and Evans ('22), Vogt ('31, '33) and others have found, moreover, that ovulation and pseudopregnancy can be induced by irritation of the cervix uteri of rabbits, rats and mice. The author tricd t o find whether the cervix was responsible for luteinizatiori in the malformed mice as well. It was attempted to demonstrate whether artificial occlusion of the genital tract would lead to similar effects a s the innate occlusion and whether the situation of the occlusion above or below the cervix as of significance. Shortly after the ligation of the vagina in six mice, overlong estrous or anestrous periods supervened in some animals. During the third month, estrus was rare or absent. A mouse, whose vagina had been cut completely across without ligation, was similarly ancstric ciuririg the third month. At autopsy, the uteri, some of which ' A t thc time of the opening of the eyes this mouse already weighed 8.5 gm. After weaning growth continurd as rapidly as before. On the 423rd dav the animiil, artive and vigorous, wax killed (8 103). Hgpophysis and suprarenals were disproportionately light (0.7 and 1.4 mg. after fixation and rinsing) cornpurrd with the body weight of 30 gin. The cortex of the suprarrnals was narrow and contained numerous fatty transformed, rouudish adrnornata. OCCLUSION OF VAGINA 453 were more than 8 mm. in thickness, were distended by a clear secretion. The suprarenals possessed, in contrast to mice with innate occlusion of the vagina, a very narrow zona reticularis. On the whole, the experiment produced conditions similar to those existing in innate vaginal occlusion, although not fully identical.2 SUMMARY A malformation in mice, consisting in the blind ending and hernia-like protrusion of the vagina, often accompanied by pseudogravidity, is described. The malformation is thought to have an hereditary basis while the pseoudopregnancy is thought to be secondary. LITERATURE CITED ASDELL,8. A. AND J. HAYYOND 1933 The effects of prolonging the life of the corpus luteum by hysterectomy i n the rabbit. Am. J. Physiol., vol. 103, pp. 600-605. BUTCHEI~, J. 1932 Regeneration in ligated ovaries and transplanted ovarian fragments of the white rat (Mu8 norvcgieus albinus). Anat. h e . , V O ~ . 54, pp. 87-104. FRIZDMAN, M. R. 1929 The mechanism of ovulation in rabbit; demonstration of humoral mechanism. Am. J. Physiol., pol. 89, pp. 438-442. KEMP,T. AND L. MARX 1936 Entwicklung von Zwergmaeusen unter dem Einfluss verschiedener Hypophysenhormone und yon Thyroxin. Aeta path. e t mierobiol. Scandinav. ( I n press.) LOEB, L. A N D ' W . €3. KOUNm 1927 The effect of folliculine on the generative organs of hystereetomized guinea pigs. Proc. Soe. Exp. Biol. and Ned., vol. 24, pp. 728-731. LONG,J. A. AND H. M. EVANS 1922 The oestrous cycle in the albino rat and its associated phenomena.. Memoirs of the Univ. of California VII. MARTINOVITCH,P. N. 1934 L a ligature temporaire des ovaires de la lapine et le problhme de l'ovogenhse post-natale chez cet animal. Compt. rend. SOC.de Biol., T. 116, pp. 1294-1297. 1935 La ligature permanente des ovaires de rats blanes et le problhme de la formation post-natale de cellules germinatives chez de Biol., T. 118, pp. 394-351. cet animal. Compt. rend. SOC. lAfter ligation of the uteri estrus prevailed, if both horns had been blocked. The experiment is however not conclusive, as injury to the vessels could not be avoided and the ovaries of one mouse (in which estrus had been rare) were much engorged. The number of primary egg cclls and small follicles waa greatly reduced in all animals. The zona reticularis of the suprarenals was broad. THE ANATOMICAL RECOED, vofi. 66, NO. 4 454 LORE MARX MASUI, H. 1926 The effect of gonadectomy on the structure of the suprarenal gland of mice with reference to the functional relation between this gland and the sex glands of the female. J. Col. Agr. Imper. Univ. Tokyo, vol. 7, no. 4. RIETSCHEL,P. E. 1929 Zur Morphologie und Histologie der Genitalausfuehrungsgaenge im Individualzyklus der weissen Maus. Zeit. f. wiss. ZOO^., Bd. 135, 8.428-494. VWT, M. 1931 Ueber den Mechanismus zur Ausloesung der Graviditaet und Pseudograviditaet, auglcich ein physiologischer Beweis fuer die sympathische Innervation des Hypophysenvorderlappens. Arch. f. path. u. Pharmakol., Bd. 162, 5. 197-208. 1933 Ueber den Mechanismus der Ausloesung der Graviditaet nnd Pseudograviditaet. 11. Mitteilung. Ibid., Bd. 170, S. 72-83. WIESNEB,B. P. 1932 Effects of early oophorectomy in rats. J. Physiol., vol. 75. p. 39P.