Nonhuman primate models of polycystic ovary syndrome.

Nonhuman primate models of polycystic ovary syndrome.
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DOI:
10.1016/j.mce.2013.01.013
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发表时间:
2013-07-05
影响因子:
4.1
通讯作者:
Dumesic DA
Dumesic DA
中科院分区:
医学2区
文献类型:
--
作者:
Abbott DH;Nicol LE;Levine JE;Xu N;Goodarzi MO;Dumesic DA

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与人类基因组和表型相似,非人类灵长类动物模型提供了多囊卵巢综合征(PCOS)的全面表观遗传模仿,提示早期生命靶向预防。在所有非人灵长类动物模拟中,胎儿暴露于睾酮(T)提供了最接近多囊卵巢综合征样表型,妊娠早期到中期暴露于睾酮的雌性恒河猴表现出成年后生殖、内分泌和代谢功能障碍特征,这些特征是多囊卵巢综合征的共同病理。妊娠晚期暴露于T,虽然会诱发成年卵巢雄激素分泌亢进和月经异常,但伴随的代谢异常较少。胎儿暴露于二氢睾酮(DHT)或己烯雌酚(DES)提示胎儿程序的雄激素和雌激素方面。新生儿接触T不会产生pcos样的结果,而持续接受T治疗的少女会导致体重过早增加和月经初潮提前(高T),或高LH和体重增加(中等T)。成年女性急性T暴露会产生多卵泡性卵巢,而慢性T暴露会引起轻微的月经不规则,但不会产生代谢功能障碍。
With close genomic and phenotypic similarity to humans, nonhuman primate models provide comprehensive epigenetic mimics of polycystic ovary syndrome (PCOS), suggesting early life targeting for prevention. Fetal exposure to testosterone (T), of all nonhuman primate emulations, provides the closest PCOS-like phenotypes, with early-to-mid gestation T-exposed female rhesus monkeys exhibiting adult reproductive, endocrinological and metabolic dysfunctional traits that are co-pathologies of PCOS. Late gestational T exposure, while inducing adult ovarian hyperandrogenism and menstrual abnormalities, has less dysfunctional metabolic accompaniment. Fetal exposures to dihydrotestosterone (DHT) or diethylstilbestrol (DES) suggest androgenic and estrogenic aspects of fetal programming. Neonatal exposure to T produces no PCOS-like outcome, while continuous T treatment of juvenile females causes precocious weight gain and early menarche (high T), or high LH and weight gain (moderate T). Acute T exposure of adult females generates polyfollicular ovaries, while chronic T exposure induces subtle menstrual irregularities without metabolic dysfunction.
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