Induction of abnormal epithelial changes by estrogen in neonatal mouse vaginal transplants

Adenosis occurred in transplanted C57BL and BALB/c mice Müllerian-derived reproductive tract regions, cervix, and/or fornix (FX), and middle vagina but never in the urogenital sinus-derived portion of the vagina, after a 1-mo exposure to endogenous ovarian hormones or exogenous estradiol (E2). Grafts in ovariectomized hosts did not exhibit adenosis, confirming its dependence on estrogen. C57BL FX and midvaginal transplants from 1-, 3-, and 5-day-old donors but not from 7- or 10-day-old donors developed adenosis, indicating a critical period before day 6. Prolonged E2 exposure (to 2 mo) decreased the adenosis incidence observed in the C57BL FX group but not in midvaginal transplants. Progesterone added during the second half of transplantation to continuing exogenous E2 prevented this reduction in the FX group; however, adenosis incidence in the similarly treated middle vagina group was less than that observed after 1 or 2 mo of E2 treatment alone. Progesterone present throughout the 2-mo transplantation period did not significantly affect adenosis incidence induced by 2-mo exposure of midvaginal or FX grafts to E2 alone. Changes suggestive of squamous cell carcinoma were found in a few BALB/c midvaginal grafts after E2 exposure for 1 mo and in some C57BL midvaginal and FX grafts after E2 and progesterone exposure for 2 mo.