Kawwass Jennifer F, Summer Ross, Kallen Caleb B
Department of Gynecology and Obstetrics, Division of Reproductive Endocrinology and Infertility, Emory University School of Medicine, 1639 Pierce Drive, WMB 4217, Atlanta, GA 30322, USA.
Center for Translational Medicine, Thomas Jefferson University, 1020 Walnut Street, Philadelphia, PA 19107, USA.
Mol Hum Reprod. 2015 Aug;21(8):617-32. doi: 10.1093/molehr/gav025. Epub 2015 May 11.
Obesity is a risk factor for infertility and adverse reproductive outcomes. Adipose tissue is an important endocrine gland that secretes a host of endocrine factors, called adipokines, which modulate diverse physiologic processes including appetite, metabolism, cardiovascular function, immunity and reproduction. Altered adipokine expression in obese individuals has been implicated in the pathogenesis of a host of health disorders including diabetes and cardiovascular disease. It remains unclear whether adipokines play a significant role in the pathogenesis of adverse reproductive outcomes in obese individuals and, if so, whether the adipokines are acting directly or indirectly on the peripheral reproductive tissues. Many groups have demonstrated that receptors for the adipokines leptin and adiponectin are expressed in peripheral reproductive tissues and that these adipokines are likely, therefore, to exert direct effects on these tissues. Many groups have tested for direct effects of leptin and adiponectin on reproductive tissues including the testis, ovary, uterus, placenta and egg/embryo. The hypothesis that decreased fertility potential or adverse reproductive outcomes may result, at least in part, from defects in adipokine signaling within reproductive tissues has also been tested. Here, we present a critical analysis of published studies with respect to two adipokines, leptin and adiponectin, for which significant data have been generated. Our evaluation reveals significant inconsistencies and methodological limitations regarding the direct effects of these adipokines on peripheral reproductive tissues. We also observe a pervasive failure to account for in vivo data that challenge observations made in vitro. Overall, while leptin and adiponectin may directly modulate peripheral reproductive tissues, existing data suggest that these effects are minor and non-essential to human or mouse reproductive function. Current evidence suggests that direct effects of leptin or adiponectin on peripheral reproductive tissues are unlikely to factor significantly in the adverse reproductive outcomes observed in obese individuals.
肥胖是不孕不育及不良生殖结局的一个风险因素。脂肪组织是一个重要的内分泌腺，可分泌大量被称为脂肪因子的内分泌因子，这些因子调节包括食欲、新陈代谢、心血管功能、免疫和生殖等多种生理过程。肥胖个体中脂肪因子表达的改变与包括糖尿病和心血管疾病在内的许多健康紊乱的发病机制有关。目前尚不清楚脂肪因子在肥胖个体不良生殖结局的发病机制中是否起重要作用，如果是，这些脂肪因子是直接还是间接作用于外周生殖组织。许多研究小组已经证明，脂肪因子瘦素和脂联素的受体在外周生殖组织中表达，因此这些脂肪因子可能对这些组织产生直接影响。许多研究小组已经测试了瘦素和脂联素对包括睾丸、卵巢、子宫、胎盘和卵子/胚胎在内的生殖组织的直接影响。生育潜力下降或不良生殖结局可能至少部分源于生殖组织内脂肪因子信号缺陷这一假说也已得到验证。在此，我们对已发表的关于两种脂肪因子——瘦素和脂联素的研究进行批判性分析，针对这两种因子已经产生了大量数据。我们的评估揭示了这些脂肪因子对外周生殖组织直接影响方面存在显著的不一致性和方法学局限性。我们还观察到普遍存在未能考虑到挑战体外观察结果的体内数据的情况。总体而言，虽然瘦素和脂联素可能直接调节外周生殖组织，但现有数据表明这些影响较小，对人类或小鼠的生殖功能并非必不可少。目前的证据表明，瘦素或脂联素对外周生殖组织的直接影响不太可能在肥胖个体中观察到的不良生殖结局中起重要作用。
