Sorbonne Universités, UPMC University Paris 06, UMR 7224Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 952 and Centre National de la Recherche Scientifique (CNRS) UMR 7224, Physiopathologie des Maladies du Système Nerveux Central (PMSNC), Université Pierre et Marie Curie, <br/>9 Quai St Bernard Bât B 2ème Étage, F75005 Paris, France Institut National de la Recherche Agronomique (INRA) UMR85, Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France CNRS UMR 7247, F-37380 Nouzilly, France Université François Rabelais, F-37000 Tours, France.
J Endocrinol. 2014 Feb 10;220(3):375-88. doi: 10.1530/JOE-13-0607. Print 2014 Mar.
Bisphenol A (BPA) is a widespread estrogenic compound. We investigated the effects of maternal exposure to BPA at reference doses on sexual behavior and neuroendocrine functions of female offspring in C57BL/6J mice. The dams were orally exposed to vehicle alone or vehicle-containing BPA at doses equivalent to the no observed adverse effect level (5 mg/kg body weight per day) and tolerable daily intake (TDI, 0.05 mg/kg body weight per day) level from gestational day 15 until weaning. Developmental exposure to BPA increased the lordosis quotient in naive females exposed to BPA at the TDI dose only. BPA exposure had no effect on olfactory preference, ability to express masculine behaviors or number of calbindin-positive cells, a sexually dimorphic population of the preoptic area. BPA at both doses selectively increased kisspeptin cell number in the preoptic periventricular nucleus of the rostral periventricular area of the third ventricle in adult females. It did not affect the number of GNRH-positive cells or percentage of kisspeptin appositions on GNRH neurons in the preoptic area. These changes were associated with higher levels of estradiol (E2) at the TDI dose while levels of LH, estrus cyclicity, ovarian and uterine weights, and fertility remained unaffected. Delay in the time of vaginal opening was observed during the postnatal period at TDI dose, without any alteration in body growth. This shows that developmental exposure to BPA at reference doses did not masculinize and defeminize the neural circuitry underlying sexual behavior in female mice. The TDI dose specifically exacerbated responses normally induced by ovarian E2, through estrogen receptor α, during the postnatal/prepubertal period.
双酚 A (BPA) 是一种广泛存在的雌激素化合物。我们研究了母体在参考剂量下暴露于 BPA 对 C57BL/6J 小鼠雌性后代性行为和神经内分泌功能的影响。从妊娠第 15 天到断奶，母鼠经口单独暴露于载体或含有相当于无观察到不良效应水平（5mg/kg 体重/天）和可耐受日摄入量（TDI，0.05mg/kg 体重/天）的 BPA 载体。发育暴露于 BPA 仅在 TDI 剂量下增加了对 BPA 暴露的未成熟雌性的屈服商数。BPA 暴露对嗅觉偏好、表达雄性行为的能力或 calbindin 阳性细胞的数量没有影响，calbindin 阳性细胞是视前区的一种性别二态细胞。在两种剂量下，BPA 选择性地增加了成年雌性第三脑室前脑室周围核的前脑室室周核中 kisspeptin 细胞的数量。它不影响前脑区 GnRH 阳性细胞的数量或 kisspeptin 在 GnRH 神经元上的附着比例。这些变化与 TDI 剂量下更高水平的雌二醇 (E2) 相关，而 LH、发情周期、卵巢和子宫重量以及生育能力保持不变。在 TDI 剂量下，观察到幼鼠期阴道开口时间延迟，但身体生长没有任何改变。这表明，在参考剂量下发育暴露于 BPA 并没有使雌性小鼠的性行为神经回路雄性化或雌性化。TDI 剂量特别加剧了在产后/青春期期间由卵巢 E2 通过雌激素受体 α 正常诱导的反应。
