Sex differences and effects of prenatal exposure to excess testosterone on ventral tegmental area dopamine neurons in adult sheep.
Sex differences and effects of prenatal exposure to excess testosterone on ventral tegmental area dopamine neurons in adult sheep.
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DOI：
10.1111/ejn.12871
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发表时间：
2015-05
期刊：
影响因子：
--
通讯作者：
Coolen LM
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文献类型：
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作者：
Brown EC;Steadman CJ;Lee TM;Padmanabhan V;Lehman MN;Coolen LM
绵羊产前睾酮(T)过量导致广泛的生殖神经内分泌缺陷和动机行为的改变。腹侧被盖区（VTA）在奖励和动机行为中起着至关重要的作用，并且被假设为产前t的目标。在这里，我们报告了成年羊的VTA多巴胺细胞数量的性别差异，雄性的酪氨酸羟化酶（TH）免疫反应细胞数量高于雌性。此外，与对照母羊相比，在妊娠期30-90天和60-90天产前暴露于过量的T会导致成年母羊VTA TH免疫反应细胞数量增加。体视学分析证实，雄性和产前接受t治疗的母羊的VTA中神经元数量显著增加，这主要是由于th免疫反应细胞数量增加。此外，男性和产前接受T治疗的女性细胞中TH的免疫反应性更强，这表明性别差异和产前暴露于过量T会影响表达TH的细胞数量以及多巴胺细胞的蛋白水平。黑质中th免疫反应细胞的数量也存在性别差异，男性的细胞多于女性。然而，产前暴露于过量的T并不影响黑质中th免疫反应细胞的数量，这表明这种性别差异是独立于产前T的作用而组织的。总之，这些结果表明绵羊VTA多巴胺系统的性别差异被产前过量的T处理所模仿。
Prenatal testosterone (T) excess in sheep results in a wide array of reproductive neuroendocrine deficits and alterations in motivated behavior. The ventral tegmental area (VTA) plays a critical role in reward and motivated behaviors and is hypothesized to be targeted by prenatal T. Here we report a sex difference in the number VTA dopamine cells in the adult sheep with higher numbers of tyrosine hydroxylase (TH)-immunoreactive cells in males than females. Moreover, prenatal exposure to excess T during either gestational days 30–90 or 60–90 resulted in increased numbers of VTA TH- immunoreactive cells in adult ewes compared to control females. Stereological analysis confirmed significantly greater numbers of neurons in the VTA of males and prenatal T-treated ewes, which was primarily accounted for by greater numbers of TH-immunoreactive cells. In addition, immunoreactivity for TH in the cells was denser in males and prenatal T-treated females, suggesting that sex differences and prenatal exposure to excess T affects both numbers of cells expressing TH as well as the protein levels with dopamine cells. Sex differences were also noted in numbers of TH-immunoreactive cells in the substantia nigra, with more cells in males than females. However, prenatal exposure to excess T did not affect numbers of TH-immunoreactive cells in the substantia nigra, suggesting that this sex difference is organized independently from prenatal actions of T. Together, these results demonstrate sex differences in the sheep VTA dopamine system which are mimicked by prenatal treatment with excess T.