POLYCYSTIC OVARY SYNDROME: ORIGINS AND IMPLICATIONS: Polycystic ovary syndrome: an evolutionary metabolic adaptation
Year: 2025
Type: review
Abstract: In brief: 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. Abstract: 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.
Source: Reproduction
DOI: 10.1530/rep-25-0021
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Institutes of Health, Oregon National Primate Research Center, National Institute of Environmental Health Sciences, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Clinical and Translational Science Institute, University of California, Los Angeles
Awards: G1989138724, G2185458402, Genes, Androgens and Intrauterine Environment in PCOS, Hyperandrogenemia, Diet and Female Reproductive Health, G3077957717, G562934659, Prenatal Programming of Reproductive Health and Disease, Reproductive Consequences of Steroid Hormone Administration, Whole exome analyses in naturally occurring hyperandrogenic female monkeys, Wisconsin National Primate Research Center Support, Support for National Primate Research Center, Michigan Center on Lifestage Environmental Exposures and Disease (M-LEEaD), UCLA Clinical and Translational Science Institute
OpenAlex ID: W4408403607