Development of polycystic ovary syndrome: involvement of genetic and environmental factors
Development of polycystic ovary syndrome: involvement of genetic and environmental factors
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DOI：
10.1111/j.1365-2605.2005.00623.x
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发表时间：
2006-02-01
影响因子：
--
通讯作者：
Hardy, K
中科院分区：
文献类型：
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作者：
Franks, S;McCarthy, MI;Hardy, K
我们最近提出，多囊卵巢综合征（PCOS）有其起源于胎儿生活。这一假设基于动物模型（产前暴露于高剂量雄激素的恒河猴或绵羊）的数据，并得到临床研究的支持。这表明，在人类女性中，暴露于过量的雄激素，在任何阶段，从胎儿的卵巢发育到青春期的开始，导致PCOS的许多特征，包括黄体生成素分泌异常和胰岛素抵抗。在PCOS患者中，PCOS表型的发生可能主要是由于胎儿卵巢过度分泌雄激素的遗传易感性。目前尚不清楚母体环境是否直接影响后代多囊卵巢综合征的发展。母体雄激素过多不太可能影响胎儿，因为胎盘提供了一个有效的屏障，但妊娠期间的代谢紊乱可能会影响胎儿综合征的发展。在出生后的生活中，PCOS的自然史可以通过影响胰岛素分泌和/或作用的因素进一步改变，最重要的是营养。我们现在有证据表明，多囊卵巢的早期卵泡发育障碍与胎儿卵巢原始卵泡数量增加一致。这一现象是否是卵巢内雄激素暴露增加的原因或结果仍有待确定。PCOS是女性最常见的内分泌疾病。它不仅是无排卵性不孕症、月经失调和多毛症的一个非常普遍的原因，而且也是晚年发展为2型糖尿病的一个主要危险因素。该综合征的病因仍不确定，但有越来越多的证据表明是遗传基础。多囊卵巢综合征通常在青春期随着下丘脑-垂体-卵巢轴的成熟而临床表现出来，但该综合征的发生可能在非常早期的发育过程中-甚至可能在子宫内。在这篇综述中，这一假说是探讨在临床，生化和遗传学研究的光。
We have recently proposed that polycystic ovary syndrome (PCOS) has its origin in fetal life. This hypothesis is based on data from animal models (rhesus monkey or sheep that have been exposed prenatally to high doses of androgen) and is supported by clinical studies. It is suggested that, in human females, exposure to excess androgen, at any stage from fetal development of the ovary to the onset of puberty, leads to many of the characteristic features of PCOS, including abnormalities of luteinizing hormone secretion and insulin resistance. It is likely that, in humans with PCOS, the development of the PCOS phenotype results primarily from a genetic predisposition for the fetal ovary to hypersecrete androgen. At present, it is unclear whether the maternal environment directly influences the development of PCOS in the offspring. Maternal androgen excess is unlikely to affect the fetus, because the placenta presents an effective barrier, but metabolic disturbances during pregnancy could affect development of the syndrome in the fetus. In postnatal life, the natural history of PCOS can be further modified by factors affecting insulin secretion and/or action, most importantly, nutrition. We now have evidence for a disorder of early follicular development in the polycystic ovary that is consistent with an increased population of primordial follicles in the fetal ovary. It remains to be determined whether this phenomenon is the cause or the effect of increased exposure to androgen within the ovary. PCOS is the commonest endocrine disorder in women. It is not only a very prevalent cause of anovulatory infertility, menstrual disturbances and hirsutism, but it is also a major risk factor for the development of type 2 diabetes mellitus in later life. The aetiology of the syndrome remains uncertain but there is increasing evidence for a genetic basis. PCOS very often becomes clinically manifest during adolescence with maturation of the hypothalamic-pituitary-ovarian axis but the genesis of the syndrome may be during very early development - perhaps even in utero. In this review, this hypothesis is explored in the light of clinical, biochemical and genetic research.