Critical period of induction by tamoxifen of genital organ abnormalities in female mice.

Genital organs of C57BL/Tw female mice given 5 daily injections of 100 micrograms tamoxifen (Tx) from the day of birth (day 0) were examined at 5, 10, 15, 20, 30 and 60 days of age. The incidence of polyovular follicles (PF) in Tx mice was higher, but the development of uterine glands and tunica muscularis uteri in Tx mice was lower than in the age-matched controls. Uteri of 15-day-old Tx mice underwent a weight increase resulting from edematous change in the stromal tissue lacking type I collagen and fibronectin. Adenosis-like lesions were found in the vaginae of 5- to 30-day-old Tx mice. Mice given neonatal injections of 100 micrograms clomiphene (Clm) and nafoxidine (Naf) were also examined at 60 days. Tx caused much greater damage to the ovary and uterus than did Clm and Naf. In order to examine the critical period of induction by Tx of female genital organ abnormalities, mice were given 5 daily injections of Tx starting at different early postnatal ages. Tx injections starting within 5 days caused a high incidence of PF in the ovary and aplasia of tunica muscularis in the uterus. The Tx treatment also induced atrophy of the uterine luminal epithelium when started within 7 days. The present study suggests, therefore, that the postnatal limit of the critical period for the female genital organs lies within 7 days after birth.