Institute for Neuroscience, The University of Texas at Austin, Austin, Texas.
Department of Psychology, The University of Texas at Austin, Austin, Texas.
J Exp Zool A Ecol Integr Physiol. 2020 Oct;333(8):550-560. doi: 10.1002/jez.2404. Epub 2020 Aug 15.
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.
发育中的大脑对激素环境高度敏感，性腺类固醇激素参与神经发生、神经存活和大脑组织。有限的可用证据表明，内分泌干扰化学物质（EDCs）可能会扰乱这些发育过程。在这项研究中，我们假设产前暴露于多氯联苯（PCBs）混合物 Aroclor 1221 会破坏两个下丘脑区域的神经发生正常时间：腹内侧核（VMN）和视前区（POA）。选择这些区域是因为它们在控制社会性行为方面具有重要作用，而产前 EDC 暴露会扰乱成年后的社会性行为。怀孕的 Sprague-Dawley 大鼠从胚胎第 8 天（E8）到第 18 天（E18）暴露于 PCBs，包括所有下丘脑神经元的神经发生时期。为了确定神经元的出生日期，在 E12、E14 或 E16 时向母体注射溴脱氧尿苷（BrdU）。出生后的第一天，雄性和雌性幼崽被灌注、BrdU 免疫标记，并计数细胞数量。在 VMN 中，与载体处理的幼崽相比，PCBs 显著提前了神经发生的时间，而不改变 BrdU+细胞的总数。在 POA 中，PCBs 既不改变神经发生的时间也不改变出生细胞的总数。这是第一项表明 PCBs 可以改变下丘脑神经发生时间的研究，特别是在 VMN 中，但不在 POA 中。这一结果对 VMN 控制的功能，特别是社会性行为，以及更广泛的性选择具有重要意义。
