Sex differences and the development of the rabbit brain: Effects of vinclozolin
Sex differences and the development of the rabbit brain: Effects of vinclozolin
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DOI：
10.1095/biolreprod.106.052795
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发表时间：
2006-09-01
影响因子：
3.6
通讯作者：
Tobet, Stuart
中科院分区：
文献类型：
--
作者：
Bisenius, Erin S.;Veeramachaneni, D. N. Rao;Tobet, Stuart
视前区/下丘脑前区（POA/AH）是脊椎动物脑中最具性二态性的区域之一，在调节雄性性行为中起着关键作用。阿米洛唑林是一种杀真菌剂，被认为是一种环境抗雄激素，在发育期间给予兔子时会破坏雄性性行为。在这项研究中，我们研究了几个特点的兔POA/AH的性二型和内分泌干扰vinclozolin。从妊娠中期开始，妊娠兔每天一次经口给予乙烯氯唑啉（10 mg/kg体重）或胡萝卜糊溶剂，持续6周，并持续至产后第4周。在6周，后代灌注4%多聚甲醛和大脑处理酪氨酸羟化酶，钙结合蛋白，促性腺激素释放激素（GnRH），或尼氏染色的免疫细胞化学定位。有显着的性别差异，在POA/AH的钙结合蛋白的分布和背侧POA/AH的细胞的大小（女性的值大于男性），但在酪氨酸羟化酶或GnRH神经元的数量或分布。在两种性别中，暴露于vinclozolin显着增加钙结合蛋白的腹侧POA/AH的表达和显着减少GnRH神经元的数量选择性的终板（OVLT）的血管器的区域，但不是更尾部的POA/AH。这是第一个文件的性二型区域在兔脑，并进一步支持使用这个物种作为模型研究的影响，乙烯唑啉对生殖发育与潜在的应用到人类系统。
The preoptic/anterior hypothalamic area (POA/AH) is one of the most sexually dimorphic areas of the vertebrate brain and plays a pivotal role in regulating male sexual behavior. Vinclozolin is a fungicide thought to be an environmental antiandrogen, which disrupts masculine sexual behavior when administered to rabbits during development. In this study, we examined several characteristics of the rabbit POA/AH for sexual dimorphism and endocrine disruption by vinclozolin. Pregnant rabbits were dosed orally with vinclozolin (10 mg/kg body weight) or carrot paste vehicle once daily for 6 wk beginning at midgestation and continuing through nursing until Postpartum Week 4. At 6 wk, offspring were perfused with 4% paraformaldehyde and brains processed for immunocytochemical localization of tyrosine hydroxylase, calbindin, gonadotropin-releasing hormone (GnRH), or Nissl stain. There were significant sex differences in the distribution of calbindin in the POA/AH and the size of cells in the dorsal POA/AH (values greater in females than in males), but not in the number or distribution of tyrosine hydroxylase or GnRH neurons. In both sexes, exposure to vinclozolin significantly increased calbindin expression in the ventral POA/AH and significantly decreased number of GnRH neurons selectively in the region of the organum vasculosum of the lamina terminalis (OVLT) but not more caudally in the POA/AH. This is the first documentation of a sexually dimorphic region in the rabbit brain, and further supports the use of this species as a model for studying the influence of vinclozolin on reproductive development with potential application to human systems.