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Induction of Abnormal Epithelial Changes by Estrogen in Neonatal Mouse Vaginal Transplants¹

Department of Zoology and Cancer Research Laboratory, University of California, Berkeley, California 94720

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.

¹ This investigation was supported by USPHS Grant CA05388 awarded by the National Cancer Institute, Department of Health and Human Services.

² Present address: Department of Biology, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236, Japan.

³ To whom requests for reprints should be addressed.

Received 11/19/84. Revised 5/23/85. Accepted 7/18/85.