STUDIES ON MALFORMATION OF UROGENITAL TRACT REPORT 4

EXPERIMENTAL STUDY ON INTERSEX

Abstract

Fifty three DD strain pregnant mice were administered with 0.5-50mg. of testosterone propionate on the 7th-9th day of prgnancy, 12th-14th, 15th-17th and 20th-21st day of pregnancy and as the result 59 female child mice were obtained. Serial section preparations were made from this material and a reconstruction of the entire genital organs was conducted. These were subjected to a continuous detailed investigation and the following results were obtained.
1. Androgens administered to the mother after the 12th day of pregnancy acted as a teratogenic agent which exerted its action selectively on the genital organs of the female fetus and it was shown that it did not cause bodily changes such as changes in body weight or gross abnormalities in shape. However, androgens administered prior to the 9th day of pregnancy cause numerous cases of absorbing of the embryo or deaths of fetuses. In other words androgens exert their effects as a lethal agent rather than being a teratogenic agent against the embryo.
2. The changes in the female genital organs were seen in the ovary, Wolffian ducts, urogenital sinus and external genitalia. A definite degeneration of the normal medullary structure of the ovary and instead of this a development of the seminiferous tubule like structure were seen, while the Wolffian ducts rather than showing a regression showed a develpoment which exceeded reports hitherto. And there were even some cases in which the development came to the same degree as seen in normal male mice. In the urogenital sinus also, a marked and highly frequent incidence of development of prostate like structure and atrophy of the vagina was seen. The phallus showed the highest degree of sensitivity to androgens and administration after the 12th day of pregnancy showed an almost invariable enlargement and elongation together with a development of cavernous body.
3. In regards to the entire genital organ, an increasingly remarkable and frequent masculinisation was seen the closer to the caudal portion and the farther from the cranial portion showing a tendency of the so-called CAUDAD-CEPHALAD GRADIENT OF SENSITIVITY.
4. An intimate relationship was seen between the time of androgen administration and the incidence frequency of malformation. In the present experiments the most remarkable and frequent incidence of malformations was seen in the group administered with androgen on the 12th-17th days of pregnancy. In other words this period is the CRITICAL PERIOD for malformation.
From the above animal experiments it is clear that when the pregnant mother is administered with androgens, genital abnormalities in the female offspring develop. Thus, it may be conjectured that androgen may become a teratogenic agent in human beings.