Lactational polychlorinated biphenyls exposure induces epigenetic alterations in the Leydig cells of progeny rats

The present study was designed to establish the epigenetic mechanisms by which lactational exposure to PCBs affects the Leydig cell function in progeny rats. The lactating dams were oral gavaged with different doses of PCBs [1, 2 and 5 mg/kg or corn oil ] and Leydig cells were isolated from the testes of progeny rats at postnatal day (PND) 60. We assessed the expression of transcription factors regulating steroidogenic machinery and the promoter methylation of LHR and AR in the Leydig cells. Our results confirmed hypermethylation of SF-1, Sp1/3, LHR and AR genes. There was a significant reduction in the gene expression of SF-1 and Sp1. The mRNA expression of Sp3 was decreased. Interestingly, there was an increased gene expression levels of DNA methyltransferases (Dnmts) (Dnmt1, Dnmt3a/b and Dnmt3l) and unaltered histone deacetylase-1 (Hdac-1). Furthermore, increased percentage of 5-methylcytosine was observed in PCBs exposed Leydig cells. Taken together, our findings suggest that promoter hypermethylation of SF-1, Sp1/3, LHR and AR could have led to transcriptional repression of these genes in Leydig cells. In conclusion, our study demonstrates that lactational exposure to PCBs caused epigenetic changes in the Leydig cells which could have impaired the Leydig cell function in progeny (PND60) rats.