Prenatal programming of reproductive neuroendocrine function: Fetal androgen exposure produces progressive disruption of reproductive cycles in sheep
Prenatal programming of reproductive neuroendocrine function: Fetal androgen exposure produces progressive disruption of reproductive cycles in sheep
复制标题
DOI：
10.1210/en.2002-220965
复制
发表时间：
2003-04-01
期刊：
影响因子：
4.8
通讯作者：
Robinson, JE
中科院分区：
文献类型：
--
作者：
Birch, RA;Padmanabhan, V;Robinson, JE
在性腺中，出生前雄激素化的母羊睾酮会导致循环 LH 的性早熟升高，并消除 LH 激增机制。本研究在卵巢完整的女性中测试了该模型的两个预测：1）产前雄激素暴露产生早期卵巢刺激； 2) 尽管进行了早期卵巢刺激，但由于 LH 激增的消除或中断，孕激素周期不会发生。怀孕母羊从妊娠第30-90天（T60组；100毫克/注射）或第60-90天（T30组；80毫克/注射）每周注射丙酸睾酮两次（足月，147天）。对照母羊不接受注射。出生时，将雄激素化羔羊和对照羔羊分为两组：卵巢完整组，以确定产前雄激素对青春期时间和随后卵巢功能的影响；卵巢切除组，以评估青春期雌激素负反馈敏感性下降和随后 LH 增加的时间。新生儿睾丸切除、接受雌激素治疗的男性也被纳入其中，以比较青春期 LH 分泌上升的时间。雄激素化女性的神经内分泌青春期（根据 LH 增加确定）提前至与男性相似的年龄。卵巢完整的母羊中出现了相同持续时间和数量的重复黄体酮周期，并且它们与对照母羊同时开始，从而否定了这两个预测。差异出现在第二个繁殖季节，此时繁殖周期要么缺失（T60），要么被破坏（T30组）。我们的研究结果表明，子宫内暴露于雄激素会导致成年后循环功能逐渐丧失。
In the agonadal, androgenized ewe testosterone before birth produces a precocious pubertal rise in circulating LH and abolishes the LH surge mechanism. The present study tested two predictions from this model in the ovary-intact female: 1) prenatal androgen exposure produces early ovarian stimulation; and 2) despite early ovarian stimulation, progestogenic cycles would not occur because of the abolition or disruption of the LH surge. Pregnant ewes were injected with testosterone propionate twice per week from either d 30-90 (T60 group; 100 mg/injection) or d 60-90 (T30 group; 80 mg/injection) of gestation (term, 147 d). Control ewes received no injections. At birth, the androgenized and control lambs were divided into two groups: ovary-intact to determine the effects of prenatal androgen on the timing of puberty and subsequent ovarian function, and ovariectomized to assess the timing of the pubertal decrease in sensitivity to estrogen negative feedback and the subsequent increase in LH. Neonatally orchidectomized, estrogen-treated males were included for comparison of the timing of this pubertal rise in LH secretion. Neuroendocrine puberty (determined on the basis of LH increase) was advanced in the androgenized females to a similar age as in males. Repeated progesterone cycles of the same duration and number occurred in the ovary-intact ewes, and they began at the same time as for control females, thus negating both predictions. Differences appeared during the second breeding season, when reproductive cycles were either absent (T60) or disrupted (T30 group). Our findings reveal that exposure to androgens in utero causes a progressive loss of cyclic function in adulthood.