Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan.
Department of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Mol Metab. 2021 Jul;49:101189. doi: 10.1016/j.molmet.2021.101189. Epub 2021 Feb 13.
Obesity has been reported to have a modulatory effect on the ovulatory functions of patients with polycystic ovary syndrome. The role of adipokines in this obesity-associated ovulatory disturbance has not been extensively explored. In this study, the relationships between obesity, adipokine production from visceral fat, and ovarian folliculogenesis were explored in a mice model of induced obesity.
Obesity was induced in female C57BL/6 mice fed ad libitum with high-fat feed and fructose water for 4 weeks. Follicular developments in the ovaries were assessed by histopathology in these diet-induced obese mice. Changes in adipokine expression in the peri-ovarian adipose tissues were screened with an adipokine array. The adipokine with the most significant increase over time was identified. The functions of the adipokine in angiogenic processes were evaluated in a cell model of endothelial proliferation. The in vivo effects of neutralizing this adipokine using specific antibodies were assessed in the same obesity model.
A high-fat and fructose diet induced an accumulation of early ovarian follicles and a reduction in mature follicles and corpus lutea. The number of microvessels in the early follicles also decreased. The adipokine protein array of the peri-ovarian adipose tissues identified a progressive increase in IL-10 expression with the duration of the obesogenic diet. In vitro experiments in the endothelial cell model confirmed IL-10 as a disrupter of VEGF-induced angiogenesis. Administration of anti-IL-10 antibodies prevented the histopathological changes induced by the obesogenic diet and further highlighted the role of IL-10 in disrupting folliculogenesis.
Obesity may disrupt normal folliculogenesis through increased production of IL-10 in visceral fats. This relationship may help clarify the reported association between obesity and ovulatory dysfunction, which has been found in patients with polycystic ovary syndrome. However, the duration of this study was short, which limited conclusions on the long-term reproductive outcomes.
肥胖被报道对多囊卵巢综合征患者的排卵功能具有调节作用。脂肪因子在这种与肥胖相关的排卵障碍中的作用尚未得到广泛探讨。本研究旨在探讨诱导肥胖的小鼠模型中肥胖、内脏脂肪产生的脂肪因子与卵巢卵泡发生之间的关系。
通过给予 C57BL/6 雌性小鼠自由摄取高脂肪饲料和果糖水的方法诱导肥胖，为期 4 周。通过组织病理学评估这些饮食诱导肥胖小鼠的卵巢卵泡发育情况。利用脂肪因子芯片筛选卵巢周围脂肪组织中脂肪因子表达的变化。确定随时间推移表达增加最显著的脂肪因子。在血管内皮细胞增殖的细胞模型中评估该脂肪因子在血管生成过程中的作用。在相同的肥胖模型中，使用特异性抗体中和该脂肪因子，评估其在体内的作用。
高脂肪和果糖饮食导致早期卵泡积累，成熟卵泡和黄体减少。早期卵泡中的微血管数量也减少。卵巢周围脂肪组织的脂肪因子蛋白芯片确定，随着肥胖诱导饮食时间的延长，IL-10 表达逐渐增加。血管内皮细胞模型的体外实验证实，IL-10 是 VEGF 诱导血管生成的破坏者。抗 IL-10 抗体的给药可预防肥胖诱导饮食引起的组织病理学变化，并进一步强调了 IL-10 在破坏卵泡发生中的作用。
肥胖可能通过内脏脂肪中 IL-10 的产生增加来破坏正常的卵泡发生。这种关系可能有助于阐明多囊卵巢综合征患者报告的肥胖与排卵功能障碍之间的关联。然而，本研究的持续时间较短，限制了对长期生殖结果的结论。
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