ENDOGENOUS AND EXOGENOUS INFLUENCES ON MAMMALIAN MALE MEIOTIC PROPHASE
Vrooman, Lisa Anne
MetadataShow full item record
Developmental exposures to estrogenic chemicals are postulated to cause spermatogenic impairment and associated male reproductive disorders in humans. Consistent with this, male rodents exposed prenatally and/or postnatally to exogenous estrogens exhibit reductions in testis size and sperm count as adults. Because meiotic errors result in the elimination of spermatocytes, we tested the hypothesis that estrogenic exposure during testis development impairs spermatogenesis in the adult testis by increasing the frequency of meiotic errors. Male CD-1, C57BL/6J, and C3H mice were exposed neonatally (1-12 days postpartum) with oral doses of 20 or 500 ng/g/day bisphenol A, 0.25 ng/g/day ethinyl estradiol, or placebo. Our analyses of placebo males of different ages provided evidence of age-dependent differences in meiosis. Recombination was reduced in the first wave of spermatogenesis by comparison with subsequent waves of spermatogenesis in the adult, and an increased frequency of meiotic errors was observed with age. However, despite this age-related increase in errors, effective elimination of these cells prevented the production of aneuploid sperm. A comparison of exposed and placebo treated males demonstrated that developmental estrogenic exposure permanently reduced recombination in CD-1 and C3H males. Furthermore, an increase in the frequency of homologous chromosomes that failed to form a recombination site in estrogen-exposed males was evident. In contrast, no effects were observed in C57BL/6J males. Consistent with our mouse studies, we demonstrated that recombination was also significantly reduced in rams similarly exposed to bisphenol A during development. Taken together, our results demonstrate that the meiotic process is significantly influenced by paternal age, and exposure to low levels of exogenous estrogens during testis development in mammals can permanently alter spermatogenesis. Our findings support the idea that meiotic errors are an important contributor to the spermatogenic impairment caused by developmental estrogenic exposure.