Bisphenol A (BPA) is an estrogenic compound commonly used in manufacture of various consumer products. Earlier studies from our group have demonstrated that neonatal exposure of male rats to BPA causes decrease in sperm count and motility, increase in post implantation loss, ultimately leading to subfertility during adulthood. One of the factors contributing for post implantation loss is altered methylation pattern of imprinted genes. The present study was undertaken to investigate the molecular effects of neonatal exposure of male rats to BPA (2.4 μg/pup) (F0) on the methylation of H19 imprinting control region (ICR) in resorbed embryo (F1) and compared with spermatozoa of their respective sires (F0). We observed a significant down regulation in the transcript expression of Igf2 and H19 genes in BPA resorbed embryo (F1) as compared to control viable embryo. A significant hypomethylation was observed at the H19 ICR in the spermatozoa as well as in resorbed embryo sired by rats exposed neonatally to BPA. These results indicated that the aberrant methylation at ICR in spermatozoa was inherited by embryo which causes perturbation in the expression of Igf2 and H19, ultimately leading to post implantation loss. This could be one of the possible mechanisms of BPA induced adverse epigenetic effects on male fertility.
In light of the adverse reports of Bisphenol A (BPA) on reproduction and considering the pivotal role played by the steroid receptors (SRs) and their coregulators in male reproduction, it was of interest to decipher the influence that BPA may have on their expression pattern during critical 'windows' of development. Male rats were injected with 2.4 µg per pup per day of BPA from postnatal days (PND) 1-5 and controls received vehicle. During development, the testicular expression pattern of SRs (AR, ERβ and ERα), coactivators (SRC-1, SRC-2 and SRC-3) and corepressors (NCoR and SMRT) in BPA-exposed rats were compared. A significant decrease in the expression of SRs was seen in the BPA group. SRC-1 showed a significant decrease, whereas SRC-2 and SRC-3 showed a significant increase in the protein expression whereas corepressor expression remained unaltered in the BPA-exposed groups. Such impairments in the expression pattern can be a putative mechanism of adversities on fertility as a result of BPA exposure.
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