Neonatal genistein or bisphenol-A exposure alters sexual differentiation of the AVPV
Neonatal genistein or bisphenol-A exposure alters sexual differentiation of the AVPV
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DOI：
10.1016/j.ntt.2005.11.004
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发表时间：
2006-01-01
影响因子：
2.9
通讯作者：
Polston, EK
中科院分区：
文献类型：
--
作者：
Patisaul, HB;Fortino, AE;Polston, EK
越来越多的人担心，天然存在的和化学制造的内分泌活性化合物（EAC）可能会破坏中枢神经系统发育过程中的神经依赖性事件。我们研究了出生后暴露于植物雌激素染料木黄酮（GEN）或塑料成分双酚A（BIS）是否影响大鼠下丘脑前腹侧室周核（AVPV）的性分化。AVPV在啮齿类动物中存在性别分化。雌性AVPV比雄性AVPV大，并且含有更多数量的表达酪氨酸羟化酶（TH）的细胞。Y\VPV的性别分化是由于雄性神经系统暴露于出生后最初几天分泌的睾丸睾酮芳香化的雌激素。因此，我们假设在此关键时期暴露于EAC可以改变AVPV中TH的性二态表达和雌激素受体α（ER α）的总体表达。在出生后第1天和第2天，每隔12小时皮下注射4次芝麻油（对照）、50 μ g 17 β-雌二醇（E-2）、250 μ g GEN或250 μ g BIS，并在出生后第19天处死动物。E-2处理使雌性AVPV中的TH免疫反应性（TH-ir）雄性化，而暴露于GEN或BIS使雄性AVPV中的TH-ir去雄性化。此外，我们鉴定了主要位于AVPV内侧区的共表达TH和ER α的神经元群体。正常情况下，女性的双标记细胞几乎是男性的三倍，但它们的数量被E-2，GEN或BIS处理去受精。这些结果表明，急性暴露于EAC在一个关键的发展时期改变AVPV的发展。(c)2005年爱思唯尔公司All rights reserved.
There is growing concern that naturally occurring and chemically manufactured endocrine-active compounds (EACs) may disrupt hormone-dependent events during central nervous system development. We examined whether postnatal exposure to the phytoestrogen genistein (GEN) or the plastics component bisphenol-A (BIS) affected sexual differentiation of the anteroventral periventricular nucleus of the hypothalamus (AVPV) in rats. The AVPV is sexually differentiated in rodents. The female AVPV is larger than the male AVPV and contains a higher number of cells expressing tyrosine hydroxylase (TH). Sexual differentiation of the Y\VPV results from exposure of the male nervous system to estrogen aromatized from testicular testosterone secreted in the first few days after birth. Thus, we hypothesized that exposure to EACs during this critical period could alter the sexually dimorphic expression of TH and the overall expression of estrogen receptor alpha (ER alpha) in the AVPV. Animals were given 4 subcutaneous injections of sesame oil (control), 50 mu g 17 beta-estradiol (E-2), 250 mu g GEN, or 250 mu g BIS at 12-h intervals over postnatal days (PND) 1 and 2 and sacrificed on PND 19. E-2 treatment masculinized TH immumoreactivity (TH-ir) in the female AVPV while exposure to GEN or BIS demasculinized TH-ir in the male AVPV In addition, we identified a population of neurons co-expressing TH and ER alpha located primarily in the medial region of the AVPV. Normally, females have nearly three times as many double-labeled cells as males, but their numbers were deferminized by E-2, GEN or BIS treatment. These results suggest that acute exposure to EACs during a critical developmental period alters AVPV development. (c) 2005 Elsevier Inc. All rights reserved.