Effect of “in utero” and lactation exposure to PCB on the expression of testosterone metabolizing enzymes in male and female rats

Aim: Polychlorinated biphenyls (PCBs) are pollutants detected in several tissues and in breast milk. They cross the placental barrier, accumulate in the brain of developing fetuses and affect the normal brain sexual differentiation by still unclear mechanisms. Hypothalamic aromatase (ARO) and the two 5alpha-reductases (5A-R1, 5A-R2), are the main enzymatic pathways that produce testosterone active metabolites. These are important organizational factors of rat brain sex differentiation and are involved in the activation of sex-specific behaviors in adulthood. Aim of this study was to verify whether “in utero” and lactation exposure to a mixture of the main PCB congeners present in high concentrations in animal food and milk might interfere with ARO, 5A-R1 and 5A-R2 hypothalamic expression from gestation to adulthood. Methods: Pregnant rats and dams were treated s.c. daily from day 15 to 19 of gestation (GD) and then twice a week till weaning (postnatal day 21, PN21) with 3 mg/kg of PCB 138, 153 and 180 and 1 microg/kg of PCB 126. ARO, 5A-R1 and 5A-R2 expression was quantified by real time PCR in the hypothalamus of prenatal (GD20), weaned (PN21) and adult (PN60) male and female rats. Results: PCB exposure during gestation and lactation is able to interfere with the normal expression pattern of all the enzymes considered in a time and sex-specific manner. In particular, these pollutants disrupt the normal pattern of ARO expression in males with no effect in females, decrease 5A-R1 more consistently in females, increase 5AR-2 expression only in adult females. Conclusion: Although further investigations are needed to better explain the effects produced by these pollutants, our data are indicative of their important interference in brain sexual differentiation and function both in male and in female animals.