Absence of teratogenic effects of progesterone on the developing genital tract of the human female fetus

Abstract

It has been questioned whether prenatal exposure to progesterone, like exposure to diethylstilbestrol (DES), results in teratogenic abnormalities of the upper and lower genital tract in human females. Through the use of a recently described model in which human fetal reproductive tracts can be transplanted and grown in vivo for extended periods in athymic nude mice, genital tracts from human female fetuses, ages 7 to 18 weeks postovulation, were grafted into castrated murine hosts and grown for 4 to 10 weeks in the presence or absence of continuous exposure to progesterone. Substantial growth was observed. For all specimens, the morphogenetic process proceeded normally, resulting in the harmonious organization of a complete, well differentiated genital tract composed of fallopian tubes, uterine corpus, and cervix and vagina. The fallopian tubes were highly convoluted and disclosed fimbria. The uterine corpus was lined by a simple columnar epithelium; two layers of stroma in the wall were distinctly separated from each other. In the older specimens, the outer layer of stroma had assumed microscopic properties diagnostic of smooth muscle (myometrium). In the majority of specimens the region of the cervix/vagina disclosed the development of a fornix-like evagination at which point or slightly cranially there was a gradual but defined transition from columnar epithelium to squamous epithelium. The inner layer of endometrial stroma tapered and disappeared at or close to the squamocolumnar junction. The vaginal stroma was a single homogeneous layer and was continuous with the myometrium of the uterine corpus. In the context of this model system, prenatal exposure of the developing human female genital tract of progesterone was not associated with any obvious teratogenic effects.