Hypermethylation of estrogen receptor promoter region in adult testis of rats exposed neonatally to bisphenol A.

作者: Tanvi Doshi , Smita Salian Mehta , Vikas Dighe , Nafisa Balasinor , Geeta Vanage

DOI: 10.1016/J.TOX.2011.07.011

关键词:

摘要: Abstract Background Bisphenol A (BPA) is an estrogenic endocrine disruptor commonly used in manufacture of polycarbonate plastics and epoxy resins. Due to its ubiquitous presence the environment, health concerns are increasing. Earlier studies from our group have shown that neonatal exposure male rats BPA affected spermatogenesis leading impairment fertility during adulthood. Further we also observed altered gene expression ERα ERβ adult testis upon exposure. Based on these results, hypothesized apart action, might mediate perturbations ERs via epigenetic mechanism. Objectives The present study was undertaken determine effect DNA methylation profile estrogen receptor promoter region machinery. Methods In order test this hypothesis, were subcutaneously injected with 2.4 μg BPA/day for first five days life, i.e., postnatal (PND) 1–5, while control received vehicle (sesame oil). Animals sacrificed adulthood (PND-125) testes dissected out analysis. Methylation pattern analyzed by bisulfite sequencing levels methyltransferases quantitative RT-PCR Western blotting respectively. Results Bisulfite revealed significant hypermethylation varying extents 40% 60%, extent 20% 65%. Approximately 2-fold increase Dnmt3a Dnmt3b at transcript protein level observed. Conclusion experimental evidence demonstrated led aberrant testis, indicating mediated changes as one possible mechanisms induced adverse effects fertility.

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