Effects of intrauterine exposure to 2,3',4,4',5-pentachlorobiphenyl on the reproductive system and sperm epigenetic imprinting of male offspring.

ABSTRACT

Polychlorinated biphenyls (PCBs) are a class of persistent organic environmental pollutants with a total of 209 homologs. The homolog 2,3',4,4',5-pentachlorobiphenyl (PCB118) is one of the most important dioxin-like PCBs and is highly toxic. PCB118 can accumulate in human tissues, serum and breast milk, which leads to direct exposure of the fetus during development. In the present study, pregnant mice were exposed to 0, 20 and 100 µg/kg/day of PCB118 during the stage of fetal primordial germ cell migration. Compared with the control group, we found morphological alterations of the seminiferous tubules and a higher sperm deformity rate in the male offspring in the treatment groups. Furthermore, the methylation patterns in the treatment groups of the imprinted genes H19 and Gtl2 in the sperm were altered in the male offspring. We also characterized the disturbance of the expression levels of DNA methyltransferase 1 (Dnmt1), Dnmt3a, Dnmt3b, Dnmt3l, and Uhrf1. The results indicated that intrauterine exposure to low doses of PCB118 could significantly damage the reproductive health of the male offspring. Therefore, attention should be paid to the adverse effects of PCB118 exposure during pregnancy on the reproductive system of male offspring.