An Evolutionary Model for the Ancient Origins of Polycystic Ovary Syndrome.
Daniel A DumesicDavid H AbbottGregorio D ChazenbalkPublished in: Journal of clinical medicine (2023)
Polycystic ovary syndrome (PCOS) is a common endocrinopathy of reproductive-aged women, characterized by hyperandrogenism, oligo-anovulation and insulin resistance and closely linked with preferential abdominal fat accumulation. As an ancestral primate trait, PCOS was likely further selected in humans when scarcity of food in hunter-gatherers of the late Pleistocene additionally programmed for enhanced fat storage to meet the metabolic demands of reproduction in later life. As an evolutionary model for PCOS, healthy normal-weight women with hyperandrogenic PCOS have subcutaneous (SC) abdominal adipose stem cells that favor fat storage through exaggerated lipid accumulation during development to adipocytes in vitro. In turn, fat storage is counterbalanced by reduced insulin sensitivity and preferential accumulation of highly lipolytic intra-abdominal fat in vivo. This metabolic adaptation in PCOS balances energy storage with glucose availability and fatty acid oxidation for optimal energy use during reproduction; its accompanying oligo-anovulation allowed PCOS women from antiquity sufficient time and strength for childrearing of fewer offspring with a greater likelihood of childhood survival. Heritable PCOS characteristics are affected by today's contemporary environment through epigenetic events that predispose women to lipotoxicity, with excess weight gain and pregnancy complications, calling for an emphasis on preventive healthcare to optimize the long-term, endocrine-metabolic health of PCOS women in today's obesogenic environment.
Keyphrases
- polycystic ovary syndrome
- insulin resistance
- adipose tissue
- fatty acid
- high fat diet
- weight gain
- healthcare
- stem cells
- body mass index
- skeletal muscle
- high fat diet induced
- metabolic syndrome
- public health
- gene expression
- type diabetes
- weight loss
- pregnant women
- risk factors
- health information
- mesenchymal stem cells
- bone marrow
- glycemic control
- blood pressure
- preterm birth
- cell therapy
- fluorescent probe
- living cells