Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.
Sci Rep. 2024 Jul 12;14(1):16082. doi: 10.1038/s41598-024-66726-2.
Regulation of physiological homeostasis, including energy balance, is thought to be modified by low levels of adult neurogenesis in the hypothalamus. Hormones such as oestradiol can influence both embryonic and adult hypothalamic neurogenic programs, demonstrating a sensitivity of hypothalamic neural progenitor cells to endogenous hormones. Previously we showed that gestational exposure to environmental levels of the xenoestrogen bisphenol A (BPA) changed neural progenitor cell behaviors in the embryo; however, we did not examine if these changes were permanent to affect adult neurogenesis. Here we investigated whether adult neuro- and/or gliogenesis were altered in mice prenatally exposed to BPA and placed on a high-fat diet challenge. Gestationally exposed adult female mice on a standard diet gained less weight than non-BPA controls, whereas gestationally exposed BPA females on a high-fat diet gained more weight than controls. Males exposed to gestational BPA showed no differences in weight gain relative to control males. Concomitantly, adult neurogenesis was increased in the VMH, DMH, and PVN of adult female mice exposed to BPA on standard diet, suggesting that disrupted adult neurogenesis might perturb normal energy balance regulation in females. These results add to growing evidence that low-dose BPA exposure in utero causes changes to adult hypothalamic function.
调节生理稳态,包括能量平衡,被认为是通过下丘脑的低水平成年神经发生来调节的。激素如雌激素可以影响胚胎和成年下丘脑的神经发生程序,表明下丘脑神经祖细胞对内源性激素敏感。之前我们表明,环境水平的外源性雌激素双酚 A(BPA)暴露于胚胎会改变神经祖细胞的行为;然而,我们没有检查这些变化是否是永久性的,以影响成年神经发生。在这里,我们研究了在高脂肪饮食挑战下,产前暴露于 BPA 的小鼠的成年神经发生和/或神经胶质发生是否发生改变。在标准饮食下,产前暴露于 BPA 的成年雌性小鼠的体重增加比非 BPA 对照组少,而在高脂肪饮食下,产前暴露于 BPA 的雌性小鼠的体重增加比对照组多。暴露于 BPA 的雄性小鼠的体重增加与对照组雄性小鼠没有差异。同时,在接受标准饮食的 BPA 暴露的成年雌性小鼠的 VMH、DMH 和 PVN 中,成年神经发生增加,这表明破坏成年神经发生可能会扰乱女性正常的能量平衡调节。这些结果增加了越来越多的证据表明,宫内低剂量 BPA 暴露会导致成年下丘脑功能发生变化。