Dumesic Daniel A, Padmanabhan Vasantha, Abbott David H
Reproduction. 2025 Mar 24;169(4). doi: 10.1530/REP-25-0021. Print 2025 Apr 1.
Polycystic ovary syndrome has ancient genetic origins that favored preferential abdominal fat accumulation, ovarian hyperandrogenism and insulin resistance. This review examines how endocrine-metabolic changes in normal-weight hyperandrogenic PCOS women originated as an evolutionary metabolic adaptation to balance enhanced fat storage with increased glucose and fatty acid availability for optimal energy use for survival and reproduction.
Polycystic ovary syndrome (PCOS) is a common endocrinopathy of reproductive-aged women, characterized by hyperandrogenism, oligo-anovulation and insulin resistance in combination with preferential abdominal fat accumulation. As an ancestral primate trait, PCOS in humans likely underwent relatively recent preferential selection when scarcity of food in hunter-gatherers of the Pleistocene selected for enhanced fat storage and insulin resistance as a survival advantage to maintain glucose homeostasis for brain and reproductive function. As an evolutional model for PCOS, healthy normal-weight women with hyperandrogenic PCOS have subcutaneous (SC) abdominal adipose stem cells that favor exaggerated lipid accumulation during adipocyte development in vitro accompanied by reduced systemic insulin sensitivity and preferential accumulation of highly lipolytic intra-abdominal fat. Programmed by genetic inheritance and epigenetic events during early life, such a metabolic adaptation in PCOS, provides a balance between enhanced SC adipose fat storage and increased circulating glucose and free fatty acid availability as energy substrate for crucial target tissues. The accompanying increased muscle strength and oligo-anovulation in PCOS women of antiquity also enabled sustained energy use during endurance activities in combination with greater time as a rearing advantage for children and a lower risk of maternal mortality. Heritable PCOS characteristics that originally evolved in primates as a genetically and epigenetically enhanced metabolic adaptation to favor fat storage now predispose to lipotoxicity and pregnancy complications, calling for improved preventive healthcare, with early lifestyle and therapeutic choices to optimize the long-term health of PCOS women and their children in today's obesogenic environment.
多囊卵巢综合征具有古老的遗传起源，有利于腹部脂肪的优先堆积、卵巢雄激素过多和胰岛素抵抗。本综述探讨了体重正常的高雄激素性多囊卵巢综合征女性的内分泌代谢变化是如何作为一种进化的代谢适应而产生的，这种适应是为了平衡脂肪储存的增加与葡萄糖和脂肪酸可用性的增加，从而为生存和繁殖提供最佳能量利用。
多囊卵巢综合征（PCOS）是育龄女性常见的内分泌疾病，其特征为雄激素过多、排卵稀少或无排卵、胰岛素抵抗以及腹部脂肪优先堆积。作为灵长类动物的一种祖传特征，人类的多囊卵巢综合征可能在更新世狩猎采集者食物短缺时经历了相对较近的优先选择，当时选择增强脂肪储存和胰岛素抵抗作为一种生存优势，以维持大脑和生殖功能的葡萄糖稳态。作为多囊卵巢综合征的一种进化模型，体重正常的高雄激素性多囊卵巢综合征健康女性具有皮下（SC）腹部脂肪干细胞，这些干细胞在体外脂肪细胞发育过程中有利于过度脂质堆积，同时伴有全身胰岛素敏感性降低和高分解代谢的腹部脂肪优先堆积。由生命早期的遗传和表观遗传事件编程，多囊卵巢综合征中的这种代谢适应在增强的SC脂肪储存与循环葡萄糖和游离脂肪酸可用性增加之间提供了平衡，这些葡萄糖和游离脂肪酸作为关键靶组织的能量底物。古代多囊卵巢综合征女性伴随的肌肉力量增加和排卵稀少或无排卵，也使得在耐力活动中能够持续利用能量，同时作为养育孩子的优势有更多时间，且降低了孕产妇死亡风险。最初在灵长类动物中作为一种遗传和表观遗传增强的代谢适应而进化的、有利于脂肪储存的可遗传多囊卵巢综合征特征，现在易导致脂毒性和妊娠并发症，这就需要改善预防性医疗保健，通过早期生活方式和治疗选择，在当今致肥胖环境中优化多囊卵巢综合征女性及其子女的长期健康。
