Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

An Evolutionary Model for Ancient Origins of Polycystic Ovary Syndrome

Version 1 : Received: 20 August 2023 / Approved: 21 August 2023 / Online: 22 August 2023 (03:23:33 CEST)

A peer-reviewed article of this Preprint also exists.

Dumesic, D.A.; Abbott, D.H.; Chazenbalk, G.D. An Evolutionary Model for the Ancient Origins of Polycystic Ovary Syndrome. J. Clin. Med. 2023, 12, 6120. Dumesic, D.A.; Abbott, D.H.; Chazenbalk, G.D. An Evolutionary Model for the Ancient Origins of Polycystic Ovary Syndrome. J. Clin. Med. 2023, 12, 6120.

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrinopathy of reproductive-aged women characterized by hyperandrogenism, oligo-anovulation and insulin resistance 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 evolutional 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 now affected by today’s contemporary environment through epigenetic events that predispose 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.

Keywords

polycystic ovary syndrome; hyperandrogenism; insulin resistance; adipocyte; adipose stem cells; evolution; body fat distribution; metabolic adaptation

Subject

Medicine and Pharmacology, Reproductive Medicine

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