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Vaginal occlusion an abnormality in mice.

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University Institute of General Pathology, Copenhagen
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
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
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-
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.
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
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.
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.
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.
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. 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
vofi. 66,
NO. 4
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.
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vaginal, mice, occlusion, abnormality
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