Abstract
Bisphenol A (BPA) and other endocrine disrupting chemicals have been reported to induce negative effects on a wide range of physiological processes, including reproduction. In the female, BPA exposure increases meiotic errors, resulting in the production of chromosomally abnormal eggs. Although numerous studies have reported that estrogenic exposures negatively impact spermatogenesis, a direct link between exposures and meiotic errors in males has not been evaluated. To test the effect of estrogenic chemicals on meiotic chromosome dynamics, we exposed male mice to either BPA or to the strong synthetic estrogen, ethinyl estradiol during neonatal development when the first cells initiate meiosis. Although chromosome pairing and synapsis were unperturbed, exposed outbred CD-1 and inbred C3H/HeJ males had significantly reduced levels of crossovers, or meiotic recombination (as defined by the number of MLH1 foci in pachytene cells) by comparison with placebo. Unexpectedly, the effect was not limited to cells exposed at the time of meiotic entry but was evident in all subsequent waves of meiosis. To determine if the meiotic effects induced by estrogen result from changes to the soma or germline of the testis, we transplanted spermatogonial stem cells from exposed males into the testes of unexposed males. Reduced recombination was evident in meiocytes derived from colonies of transplanted cells. Taken together, our results suggest that brief exogenous estrogenic exposure causes subtle changes to the stem cell pool that result in permanent alterations in spermatogenesis (i.e., reduced recombination in descendent meiocytes) in the adult male.
Highlights
Over the past few decades, there has been increasing concern that sperm counts and quality are declining [1, 2]
We show that brief exposure of newborn male mice to exogenous estrogen affects the developing spermatogonial stem cells of the testis and this, in turn, permanently alters spermatogenesis in the adult
In addition to their other potential effects on the developing brain and reproductive tract, our results suggest that estrogenic exposures can act to reduce sperm production by affecting the spermatogonial stem cell pool of the developing testis
Summary
Over the past few decades, there has been increasing concern that sperm counts and quality are declining [1, 2]. In addition to changes in sperm counts, there has been a corresponding increase in the incidence of morphological abnormalities of male reproductive organs, including hypospadias and undescended testicles as well as an increased incidence of testicular cancer [12]. This constellation of male disorders is termed testicular dysgenesis syndrome (TDS) and is postulated to be developmental in origin. TDS was originally proposed to result from exposure of the developing male to maternally-derived or environmental estrogens [13] Both correlative data from studies in humans and experimental studies using animal models have provided support for the hypothesis. Because testicular changes have not been a feature of all studies, the effect of exposures—at least for some chemicals—on the developing testis has remained controversial
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