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人类多囊卵巢综合征的啮齿动物模型。

Rodent models for human polycystic ovary syndrome.

机构信息

Andrology Laboratory, ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney, New South Wales, Australia.

出版信息

Biol Reprod. 2012 May 10;86(5):149, 1-12. doi: 10.1095/biolreprod.111.097808. Print 2012 May.

Abstract

Polycystic ovary syndrome (PCOS) is the most frequent female endocrine disorder, affecting 5%-10% of women, causing infertility due to dysfunctional follicular maturation and ovulation, distinctive multicystic ovaries and hyperandrogenism, together with metabolic abnormalities including obesity, hyperinsulinism, an increased risk of type 2 diabetes, and cardiovascular disease. The etiology of PCOS is unclear, and decisive clinical studies are limited by ethical and logistic constraints. Consequently treatment is palliative rather than curative and focuses on symptomatic approaches. Hence, a suitable animal model could provide a valuable means with which to study the pathogenesis of the characteristic reproductive and metabolic abnormalities and thereby identify novel and more effective treatments. So far there is no consensus on the best experimental animal model, which should ideally reproduce the key features associated with human PCOS. The prenatally androgenized rhesus monkey displays many characteristics of the human condition, including hyperandrogenism, anovulation, polycystic ovaries, increased adiposity, and insulin insensitivity. However, the high cost of nonhuman primate studies limits the practical utility of these large-animal models. Rodent models, on the other hand, are inexpensive, provide well-characterized and stable genetic backgrounds readily accessible for targeted genetic manipulation, and shorter reproductive life spans and generation times. Recent rodent models display both reproductive and metabolic disturbances associated with human PCOS. This review aimed to evaluate the rodent models reported to identify the advantages and disadvantages of the distinct rodent models used to investigate this complex endocrine disorder.

摘要

多囊卵巢综合征(PCOS)是最常见的女性内分泌疾病,影响 5%-10%的女性,由于卵泡成熟和排卵功能障碍、多囊卵巢和高雄激素血症以及代谢异常(包括肥胖、高胰岛素血症、2 型糖尿病和心血管疾病风险增加)导致不孕。PCOS 的病因尚不清楚,决定性的临床研究受到伦理和后勤方面的限制。因此,治疗是姑息性的,而不是治愈性的,重点是对症治疗。因此,合适的动物模型可以为研究特征性生殖和代谢异常的发病机制提供有价值的手段,并确定新的、更有效的治疗方法。到目前为止,还没有关于最佳实验动物模型的共识,该模型应理想地再现与人类 PCOS 相关的关键特征。经产前雄激素化的恒河猴表现出许多与人类状况相似的特征,包括高雄激素血症、无排卵、多囊卵巢、肥胖和胰岛素不敏感。然而,非人类灵长类动物研究的高成本限制了这些大型动物模型的实际应用。另一方面,啮齿动物模型成本低廉,提供了特征明确且稳定的遗传背景,易于进行靶向基因操作,并且具有较短的生殖寿命和世代时间。最近的啮齿动物模型显示出与人类 PCOS 相关的生殖和代谢紊乱。本综述旨在评估已报道的啮齿动物模型,以确定用于研究这种复杂内分泌疾病的不同啮齿动物模型的优缺点。

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