RESUMO
Polychlorinated biphenyls (PCBs), a kind of persistent organic pollutant, can induce hepatotoxicity in mammals. However, PCB-induced hepatotoxicity in offspring and the underlying mechanisms have been rarely studied. In the present study, Wistar rats were administered with corn oil or PCB52 (1â¯mg/kg body weight/day, by gavage) from gestational day 7 to postnatal day 21. In the PCB52-treated group, birth body lengths and weights were significantly decreased compared with the control group, suggesting developmental toxicity. Cytoplasmic injury in hepatocytes was observed in PCB52-treated male offspring, while no pathologic change was observed in female offspring, suggesting sex-biased hepatotoxicity. Furthermore, using an RNA-Seq method, coincided with the sexual bias, 454 differential expression genes (DEGs) were screened out in liver tissues of PCB52-treated male offspring, while 10 DEGs were screened out in female offspring. By KEGG annotation analysis, 4 in 12 significant pathways in male offspring were metabolism-related. In the present study, together with cytoplasmic injury of hepatocytes, decreased metabolic enzymes both at RNA and protein levels might aggravate loss of clearance capacity of hepatocytes and induce hepatotoxicity. Moreover, over-expressed peroxisome proliferator-activated receptor delta and mitogen-activated protein kinase 9 might activate apoptosis, which was verified by the augments of cleaved poly ADP-ribose polymerase 1 and caspase 3 in PCB52-treated male offspring. Taken together, PCB52 had developmental toxicity and induced sex-biased hepatotoxicity. The hepatotoxicity in male offspring might be attributed to the aggravated loss of clearance capacity and activation of apoptosis.