Increase of Anteroventral Periventricular Kisspeptin Neurons and Generation of E2-Induced LH-Surge System in Male Rats Exposed Perinatally to Environmental Dose of Bisphenol-A
Increase of Anteroventral Periventricular Kisspeptin Neurons and Generation of E2-Induced LH-Surge System in Male Rats Exposed Perinatally to Environmental Dose of Bisphenol-A
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围产期暴露于环境剂量双酚 A 的雄性大鼠前腹侧室周 Kisspeptin 神经元的增加和 E2 诱导的 LH 浪涌系统的产生
DOI：
10.1210/en.2010-1042
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发表时间：
2011-04-01
期刊：
影响因子：
4.8
通讯作者：
Chen, Ling
中科院分区：
文献类型：
--
作者：
Bai, Yinyang;Chang, Fei;Chen, Ling
围产期暴露于双酚A（BPA）的环境水平损害啮齿动物的性二态行为。大鼠前腹侧室周核（AVPV）内Kisspeptin神经元在GnRH神经元的激活和LH峰的启动中起重要作用。本研究旨在探讨围产期暴露于环境剂量BPA对雄性AVPV kisspeptin神经元和下丘脑-垂体-性腺轴发育和成熟的影响。从妊娠第10天至哺乳第7天，对雌性大鼠皮下注射2 μ g BPA/kg.d。解剖和功能的AVPV kisspeptin神经元和下丘脑-垂体-性腺轴的变化进行了检查在青春期前，青春期，和成年雄性大鼠暴露于围产期BPA（BPA大鼠）。在这里，我们表明，在出生后d（PND）30/50/90 BPA-大鼠，AVPV kisspeptin免疫反应细胞的数量持续增加，与年龄匹配的对照雄性大鼠相比。PND 30 BPA大鼠的GnRH免疫反应阳性细胞数比对照组雄性大鼠减少约40%，而PND 50/90 BPA大鼠的GnRH免疫反应阳性细胞数以G蛋白偶联受体54依赖的方式增加。雌二醇可诱导PND 90 BPA-大鼠和对照雌性大鼠产生稳定的LH峰，对G蛋白偶联受体54抑制剂敏感。PND 30/50 BPA-大鼠血浆LH水平高于对照组，而睾酮水平低于对照组。这些研究结果提供的证据表明，围产期暴露于环境剂量的BPA导致持续增加AVPV kisspeptin神经元在雄性大鼠，导致雌二醇诱导LH浪涌系统的产生。（内分泌学152：1562-1571，2011）
Perinatal exposure to environmental levels of bisphenol-A (BPA) impairs sexually dimorphic behaviors in rodents. Kisspeptin neurons in anteroventral periventricular nucleus (AVPV), which plays an important role in the activation of GnRH neurons and the initiation of LH-surge, have been suggested to be sexual dimorphism in rats. This study focused on exploring the influence of a perinatal exposure to an environmental dose of BPA on the development and maturation of male AVPV kisspeptin neurons and hypothalamus-pituitary-gonadal axis. Female rats were injected sc with 2 mu g BPA/kg.d from gestation d 10 through lactation d 7. Anatomical and functional changes in AVPV kisspeptin neurons and hypothalamus-pituitary-gonadal axis were examined in prepubertal, pubertal, and adult male rats exposed perinatally to BPA (BPA-rats). Here, we show that in postnatal d (PND)30/50/90 BPA-rats, the number of AVPV kisspeptin-immunoreactive cells was persistently increased in comparison with age-matched control male rats. The number of GnRH-immunoreactive cells in PND30 BPA-rats declined approximately 40% compared with control male rats, whereas that in PND50/90 BPA-rats was increased in a G protein-coupled receptor 54-dependent manner. Estradiol could induce a stable LH-surge in PND90 BPA-rats and control female rats, which was sensitive to the G protein-coupled receptor 54 inhibitor. In PND30/50 BPA-rats, plasma level of LH was higher, but the level of testosterone was lower than control male rats. These findings provide evidence that perinatal exposure to an environmental dose of BPA causes a sustained increase in AVPV kisspeptin neurons in male rats, leading to the generation of estradiol-induced LH-surge system. (Endocrinology 152: 1562-1571, 2011)