Abstract:
Polychlorinated Biphenyls (PCBs) are persistent environmental contaminants that pose a significant public health risk including reproductive toxicity partly because they are endocrine disruptors. The lipophilic nature of PCBs increases the risk of developmental exposure due to placenta and breast milk transfer. While liver is the major site for PCB metabolism, testis is known to express various drug-metabolizing enzymes, transporters, and transcription factors including nuclear receptors (together called drug-processing genes) that may serve as additional defense system. However, very little is known regarding the developmental regulation of the testicular drug-processing genes by maternal PCB exposure. Therefore, the goal of this study was to determine how maternal PCB exposure regulate drug-processing genes in testis of pups over a time course. Dams were orally exposed to the Fox River PCB mixture via peanut butter/oil at 0.1 mg/kg or 1 mg/kg body weight, or vehicle, throughout pregnancy and lactation period. RNA-Seq was conducted in testis of pups at postnatal day (PND) 28 and PND 35 (n=3/exposure group). Genes involved in spermatogenesis were differentially regulated by PCBs at both doses and at both ages. The PCB-mediated transcriptome response was weakened over time, with more dysregulated genes observed at PND 28 than PND 35. At PND 28, most of the differentially regulated drug-processing genes were up-regulated by maternal PCB exposure in a dose-response manner. This was associated with a dose-dependent increase in the mRNA expression of estrogen receptor beta (Esr2) and aryl hydrocarbon receptor. At PND 35, the PCB dose-response pattern was less prevalent. In conclusion, maternal exposure to the Fox River PCB mixture dose-dependently up-regulated various drug-processing genes in testis of the mouse offspring, but its effect appeared to be weakened over time.