Neuroendocrine and Developmental Impacts of Early Life Exposure to EDCs

Polychlorinated biphenyls (PCBs) pose a global challenge to environmental and human health. Although toxic and carcinogenic at higher exposure levels, at lower concentrations they can act as endocrine-disrupting chemicals. Individuals are more vulnerable to endocrine-disrupting effects of PCB exposures during the perinatal period, when the neuroendocrine system is developing, although assessing the full impact of PCB exposure is difficult because of the often-latent onset of adverse effects. The goal of this study was to determine developmental effects of an estrogenic PCB mixture, Aroclor 1221 (A1221), on KNDy and kisspeptin neuron numbers in the hypothalamic arcuate nucleus and anteroventral periventricular nucleus (AVPV), together with measures of hypothalamic-pituitary-gonadal hormones and postnatal development. We conducted RNAscope of kisspeptin, prodynorphin, neurokinin B, and estrogen receptor alpha genes in the P30 hypothalamus. Early-life PCBs caused small but significant changes in development (body weight and anogenital index) but had no effect on puberty. We found sex-specific effects of treatment on serum LH, FSH, and estradiol in a sex- and developmental age-dependent manner. RNAscope results revealed increased prodynorphin in the AVPV of male rats, but no effects on kisspeptin or neurokinin B in AVPV or arcuate nucleus. An unexpected species difference was found: we were unable to detect prodynorphin coexpression with kisspeptin within KNDy neurons in rats, unlike mice, sheep, and primates. These data show that early-life PCBs can induce developmental and hormonal changes that together with other reports showing latent effects on behavior and the hypothalamic-pituitary-gonadal axis, indicate adverse endocrine and neurobehavioral outcomes.