Identification of a Sensitive Period for Developmental Programming That Increases Risk for Uterine Leiomyoma in Eker Rats

Epidemiological and experimental animal studies have shown that exposure to xenoestrogens during reproductive tract development reprograms target tissues, leading to increased disease risk later in adult life. To understand what defines the critical risk period for this effect, termed developmental programming, the authors assess the sensitivity of the female reproductive tract to developmental programming during various stages of neonatal development. Eker rats, which are predisposed to develop uterine leiomyoma because of a germ-line defect in the tuberous sclerosis complex 2 (Tsc-2) tumor suppressor gene, were exposed to the xenoestrogen diethylstilbestrol (DES) on either postnatal days 3 to 5, 10 to 12, or 17 to 19, 3 important periods of reproductive tract development and differentiation. Developmental programming was observed in both carrier (Tsc-2Ek/+) and wild-type (Tsc-2 +/+) rats exposed to DES at days 3 to 5 and days 10 to 12 but not in rats exposed at days 17 to 19. Developmental programming r...