Normal development of the human female reproductive tract and alterations resulting from experimental exposure to diethylstilbestrol.

An in vivo model is described for the study of human uterovaginal development in the presence and absence of the teratogenic drug diethylstilbestrol (DES). Intact reproductive tracts from fragments of 29 human embryos and fetuses 5.0 to 17.7 weeks of age obtained after dilatation and curettage were grown for four weeks in vivo in athymic (nude) mice that were either untreated (control) or implanted subcutaneously with a DES pellet. Control specimens grown in vivo continued their anticipated morphogenesis for equivalent in-utero ages; the normal processes observed included fusion of the paired embryonic müllerian ducts into a single uterovaginal canal, stratification of endometrial and tubal mesenchyma into inner (presumptive endometrial stroma) and outer (presumptive myometrium) layers; plication of tubal and endometrial mucosa; uterine gland formation; and stratification (transformation) of the simple columnar epithelium of the vagina and cervix into a stratified squamous plate. Specimens exposed in vivo to DES exhibited anomalies, many of which mimicked those observed clinically in young women exposed prenatally to DES. Glandular epithelium (adenosis) was found in the vagina. The upper genital tract was malformed; its growth was stunted, and the inner and outer stromal layers of the uterine corpus and fallopian tubes failed to segregate. The authors conclude that the in vivo model that they describe, with its built-in controls, provides a valid approach for examining the dynamics of morphogenesis and cytodifferentiation in developing human genital tracts under experimentally regulated conditions.