Centre de Recherche en Reproduction et Fertilité, Faculté de Médécine Vétérinaire, Université de Montréal, St-Hyacinthe, Quebec, Canada.
CNRS, IFCE, INRAE, Université de Tours, PRC, Nouzilly, France.
Reproduction. 2022 May 23;164(1):R1-R9. doi: 10.1530/REP-22-0037.
Dietary stress such as obesity and short-term changes in energy balance can disrupt ovarian function leading to infertility. Adipose tissue secretes hormones (adipokines), such as leptin and adiponectin, that are known to alter ovarian function. Muscles can also secrete endocrine factors, and one such family of myokines, the eleven Fibronectin type III domain-containing (FNDC) proteins, is emerging as important for energy sensing and homeostasis. In this review, we summarize the known roles the FNDC proteins play in energy homeostasis and explore potential impacts on fertility in females. The most well-known member, FNDC5, is the precursor of the 'exercise hormone', irisin, secreted by both muscle and adipose tissue. The receptors for irisin are integrins, and it has recently been shown to alter steroidogenesis in ovarian granulosa cells although the effects appear to be species or context specific, and irisin may improve uterine and placental function in women and rodent models. Another member, FNDC4, is also cleaved to release a bioactive protein that modulates insulin sensitivity in peripheral tissues and whose receptor, ADGRF5, is expressed in the ovary. As obese women and farm animals in negative energy balance (NEB) both have altered insulin sensitivity, secreted FNDC4 may impact ovarian function. We propose a model in which NEB or dietary imbalance alters plasma irisin and secreted FNDC4 concentrations, which then act on the ovary through their cognate receptors to reduce granulosa cell proliferation and follicle health. Research into these molecules will increase our understanding of energy sensing and fertility and may lead to new approaches to alleviate post-partum infertility. In Brief: Hormones secreted by muscle cells (myokines) are involved in the adaptive response to nutritional and metabolic changes. In this review, we discuss how one family of myokines may alter fertility in response to sudden changes in energy balance.
饮食压力，如肥胖和短期能量平衡变化，可能会扰乱卵巢功能，导致不孕。脂肪组织分泌激素（脂肪因子），如瘦素和脂联素，已知会改变卵巢功能。肌肉也可以分泌内分泌因子，其中一类肌肉因子，十一型纤维连接蛋白 III 结构域蛋白（FNDC），作为能量感应和内稳态的重要组成部分正在出现。在这篇综述中，我们总结了已知的 FNDC 蛋白在能量平衡中的作用，并探讨了它们对女性生育能力的潜在影响。最著名的成员 FNDC5 是运动激素鸢尾素的前体，由肌肉和脂肪组织分泌。鸢尾素的受体是整合素，最近研究表明它可以改变卵巢颗粒细胞的类固醇生成，但这种作用似乎具有物种或背景特异性，鸢尾素可能改善女性和啮齿动物模型的子宫和胎盘功能。另一个成员 FNDC4 也被切割释放出一种生物活性蛋白，调节外周组织的胰岛素敏感性，其受体 ADGRF5 在卵巢中表达。由于肥胖妇女和处于负能量平衡（NEB）的农场动物的胰岛素敏感性都发生了改变，分泌的 FNDC4 可能会影响卵巢功能。我们提出了一个模型，即 NEB 或饮食失衡改变了血浆鸢尾素和分泌的 FNDC4 浓度，然后通过其同源受体作用于卵巢，减少颗粒细胞增殖和卵泡健康。对这些分子的研究将增加我们对能量感应和生育能力的理解，并可能导致新的方法来缓解产后不孕。概述：肌肉细胞分泌的激素（肌肉因子）参与营养和代谢变化的适应性反应。在这篇综述中，我们讨论了一类肌肉因子如何响应能量平衡的突然变化而改变生育能力。
