Prenatal Androgen Exposure Leads to Alterations in Gene and Protein Expression in the Ovine Fetal Ovary
Prenatal Androgen Exposure Leads to Alterations in Gene and Protein Expression in the Ovine Fetal Ovary
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DOI：
10.1210/en.2010-1219
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发表时间：
2011-05-01
期刊：
影响因子：
4.8
通讯作者：
Duncan, W. Colin
中科院分区：
文献类型：
--
作者：
Hogg, Kirsten;McNeilly, Alan S.;Duncan, W. Colin
女性胎儿在子宫内暴露于增加的雄激素导致成人表型，使人联想到多囊卵巢综合征。我们研究了产前雄激素是否能直接改变胎儿卵巢的结构和功能。我们检测了胎儿卵巢细胞增殖、生殖细胞体积、类固醇受体和类固醇生成酶的表达。此外，我们还研究了分化抑制剂（Ids）和SLIT/Roundabout发育途径。在第60 ~ 70天（C = 3, TP = 6）或第90天（C = 6, TP = 8），从母羊身上采集100 mg丙酸睾酮（TP）或对照(C)处理的雌性胎儿，每周2次。在第60天（C = 4, TP = 8）向胎儿侧腹单次注射TP （20 mg）或载药C，于第70天采集女性胎儿。产前和组织对胎儿卵巢形态、细胞增殖或生殖细胞体积没有影响。而在妊娠90 d时，StAR、CYP11A、CYP17和LHR的表达均有所降低。Id1免疫染色在第90天增加，Id3免疫染色在第70天增加。胎儿直接注射TP可下调卵巢CYP11A、雌激素受体α、β mRNA和ROBO1，上调CYP19、雄激素受体免疫染色、Id3 mRNA和蛋白表达。虽然在90岁时，产前雄激素作用不会导致胎儿卵巢的结构改变，但存在可能影响卵巢发育的功能改变。TP对胎儿卵巢有直接作用，这可能是多囊卵巢综合征羊模型中成年卵巢表型的原因之一。（内分泌学152:2048-2059,2011）
Exposure of a female fetus to increased androgens in utero results in an adult phenotype reminiscent of polycystic ovary syndrome. We investigated whether prenatal androgens could directly alter the structure and function of the fetal ovary. We examined fetal ovarian cell proliferation, germ cell volume, and the expression of steroid receptors and steroidogenic enzymes. In addition, we studied the inhibitors of differentiation (Ids) and the SLIT/Roundabout developmental pathways. Female fetuses were collected from ewes treated with 100 mg testosterone propionate (TP) or vehicle control (C), twice weekly from d 60 to 70 (C = 3, TP = 6) or d 90 (C = 6, TP = 8). Female fetuses were also collected at d 70 after a single injection of TP (20 mg) or vehicle C into the fetal flank at d 60 (C = 4, TP = 8). Prenatal and orgenization had no effect on fetal ovarian morphology, cell proliferation, or germ cell volume. However, there was a reduction in the expression of StAR, CYP11A, CYP17, and LHR at d90 of gestation. There was also an increase in Id1 immunostaining at d 90 and an increase in Id3 immunostaining at d 70. Direct injection of TP into the fetus down-regulated ovarian CYP11A, estrogen receptor alpha and beta mRNA, and ROBO1 and up-regulated CYP19, androgen receptor immunostaining, and Id3 mRNA and protein. Although at d 90 prenatal androgenization does not result in structural changes of the fetal ovary, there are functional changes that may impact on ovarian development. TP has direct actions on the fetal ovary, and these may contribute to the adult ovarian phenotype in the ovine model of polycystic ovary syndrome. (Endocrinology 152: 2048-2059, 2011)