Aberrant DNA methylation at Igf2-H19 imprinting control region in spermatozoa upon neonatal exposure to bisphenol A and its association with post implantation loss

Abstract

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.