Bisphenol A Induced Epigenetic Molecular Mechanism Of Male Mice Reproductive Barriers

[Objective] Bisphenol A, a kind of endocrine disruptors with weak estrogen activity, was reported inducing reproductive dysfunction in male species. However, the molecular mechanism studies of bisphenol A exposure about dynamic impact of the body and male reproductive dysgenesis are rarely. The current study was designed to exposure the neonatal mice in the environment with BPA concentration below human security dose and the lowest visible harmful dose according to the regulation. The molecule mechanism of BPA-induced dysfunction or dynamic effects in test group was detected. The influence on mice of next generation with BPA was further studied to show its mechanism in the aspect of epigenetics.[Methods] In this study, animal models were built with oral administration of BPA at the doses of 10μg/kg-d and 10 mg/kg-d. After exposed to bisphenol A 1 week,3weeks,5weeks and 10weeks, the effects of BPA were detected in aspects of body weight of mice and reproductive parameters (sperm density, sperm deformity rate and fertility). The testes were then collected and subjected to qRT-PCR to test the expression of epigenetic markers of mRNA (including Dnmtl, Dnmt3a, Dnmt3b, Dnmt3L, HAT, HDAC1, HDAC2, MBD1, MBD2, MBD3, MBD4 and MeCP2). The same process were repeated in the mice of 2nd generation.[Results] (1) The body weight and testis weight/bodyweight:compared with control group, the tends of body weight changes in 4 periods presented inverted-U-shaped; the testis weight/bodyweight rised at the postnatal 7 weeks exposed bisphenol A at the dose of 10 mg/kg-d.(2) Reproductive parameter:the sperm count, the sperm morphology and the fertility of male mice which were exposure of bisphenol A at postnatal 10weeks were all obviously decline.(3) The expression of the twelve genes at 4 periods:the expressions of Dnmtl were obviously decline at postnatal 1week,3 weeks and 10weeks;the expressions of Dnmt3a were obviously decline at postnatal 3weeks and 10weeks while significantly increased at postnatal 5weeks;the expressions of Dnmt3b were significantly increased at postnatal 5 weeks, while at postnatal lweek only the group of explosure 10mg/kg BPA showed decline;the expressions of HAT and HDAC2 were obviously rised;the expression of HDAC1 were obviously decline;the expressions of MBD1 were obviously decline at postnatal 1week and 3weeks;the expressions of MBD2 were obviously decline at postnatal 1week and 3weeks;the expressions of MBD3 in the group of explosure 10mg/kg BPA were obviously decline at postnatal 3weeks;the expressions of MBD4 in the group of explosure 10mg/kg BPA were obviously decline at postnatal 5 weeks;the expressions of MeCP2 were obviously rised in at postnatal 3weeks and 5weeks.(4) The influence on male offspring’s reproductive function:the sperm quantity and quality were all obviously decline. The expression of epigenetic markers also changed:the expression of DNMTs in the group of explosure 10mg/kg BPA were all obviously rised; the expression of HDAC1 in the group of explosure 10μg/kg BPA were all obviously decline; the expression of HAT and HDAC2 in the group of explosure 10mg/kg BPA were all obviously rised; the expression of MBD4 and MeCP2 in the group of explosure 10mg/kg BPA were all obviously rised.[Conclusion] The BPA exposure to neonatal male mice exerted a significant damage on reproductive system and induced modification in expression of the epigenetic markers. Additionally, this observed damage and modification was passed to the next generation by mice reproduction.