Effects of prepubertal exposure to xenoestrogen on development of estrogen target organs in female CD-1 mice

Background: There have been no previous reports comparing the effects of prepubertal xenoestrogen exposure on development of the reproductive tract and mammary glands in female mice. The effects of genistein (GEN), resveratrol (RES), zearalenone (ZEA), zeranol (ZER), bisphenol A (BPA) and diethylstilbestrol (DES) were examined. Materials and Methods: Beginning at 15 days of age, female CD-1 mice were administered 4 daily subcutaneous injections of 10 mg/kg/day of GEN, RES, ZEA, ZER or BPA, or 10 μg/kg/day of DES dissolved in dimethylsulfoxide (DMSO), or DMSO vehicle. Vaginal opening was checked; estrous cyclicity was monitored from 5, 9 or 21 weeks of age for 21 consecutive days; 6 animals per group were autopsied at 4, 8 and 24 weeks of age. Results: Prepubertal exposure to GEN, ZEA, ZER and DES (but not RES or BPA) accelerated puberty onset (vaginal opening). Vaginal smears indicated that all xenoestrogen-treated mice were cycling, but ZEA-, ZER- and DES-treated mice spent more time in estrus. At 4 weeks of age, absence of corpora lutea (anovulatory ovary) was observed in the untreated controls (33%, 2/6) and the GEN (50%, 3/6), RES (50%, 3/6), ZEA (100%, 6/6), ZER (100%, 6/6), BPA (83%, 5/6) and DES groups (100%, 6/6). At 8 weeks of age, absence of corpora lutea was observed in the ZEA (33%, 2/6) group. Corpora lutea were present in all mice sacrificed at 24 weeks of age. Groups that received prepubertal xenoestrogen injections exhibited no morphological abnormalities of the uterus and vagina, and exhibited mammary gland growth similar to that of the untreated controls at all time-points. Conclusion: GEN, ZEA, ZER and DES (but not RES or BPA) caused early vaginal opening; mice exposed to ZEA, ZER or DES spent more time in the estrus phase; ZEA-treated mice had a longer period of anovulatory ovary than other xenoestrogen-treated mice; however, none of the xenoestrogens tested altered the uterine or vaginal morphology or mammary gland growth.