Exposure to prenatal PCBs shifts the timing of neurogenesis in the hypothalamus of developing rats

Abstract

The developing brain is highly sensitive to the hormonal milieu, with gonadal steroid hormones involved in neurogenesis, neural survival, and brain organization. Limited available evidence suggests that endocrine‐disrupting chemicals (EDCs) may perturb these developmental processes. In this study, we tested the hypothesis that prenatal exposure to a mixture of polychlorinated biphenyls (PCBs), Aroclor 1221, would disrupt the normal timing of neurogenesis in two hypothalamic regions: the ventromedial nucleus (VMN) and the preoptic area (POA). These regions were selected because of their important roles in the control of sociosexual behaviors that are perturbed in adulthood by prenatal EDC exposure. Pregnant Sprague–Dawley rats were exposed to PCBs from Embryonic Day 8 (E8) to E18, encompassing the period of neurogenesis of all hypothalamic neurons. To determine the birth dates of neurons, bromo‐2‐deoxy‐5‐uridine (BrdU) was administered to dams on E12, E14, or E16. On the day after birth, male and female pups were perfused, brains immunolabeled for BrdU, and numbers of cells counted. In the VMN, exposure to PCBs significantly advanced the timing of neurogenesis compared to vehicle‐treated pups, without changing the total number of BrdU+ cells. In the POA, PCBs did not change the timing of neurogenesis nor the total number of cells born. This is the first study to show that PCBs can shift the timing of neurogenesis in the hypothalamus, specifically in the VMN but not the POA. This result has implications for functions controlled by the VMN, especially sociosexual behaviors, as well as for sexual selection more generally.

Effects of endocrine‐disrupting chemicals on hypothalamic oxytocin and vasopressin systems

“…Buijs et al (1980) reported that vasopressin content in the brain of developing rats increased beginning on E16, and that oxytocin content decreased from E16 to E18 but increased thereafter. It is also notable that neurogenesis in the hypothalamus of rodents occurs from mid to late gestation (Cheung et al, 2013;Hernandez Scudder et al, 2020a;Shimada & Nakamura, 1973). Therefore, our exposure window overlaps several key neurodevelopmental events involved in the generation and organization of hypothalamic neural circuits, including those involved in the control of social behaviors.…”