An Evolutionary Model for the Ancient Origins of Polycystic Ovary Syndrome

Abstract

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.

Reducing the Risk of Pre-Eclampsia in Women with Polycystic Ovary Syndrome Using a Combination of Pregnancy Screening, Lifestyle, and Medical Management Strategies

“…Polycystic ovary syndrome is a systemic metabolic and endocrine disorder that results from the disturbance of adaptive interdependent homeostatic survival networks (metabolic, immune, and neuroendocrine) [ 1 , 2 , 3 , 4 ]. Although a wide variety of theories have been proposed to explain the pathogenesis of PCOS [ 5 , 6 , 7 , 8 , 9 , 10 ], recent evolutionary models have provided a unified framework [ 1 , 2 ]. Evolutionary models characterize PCOS as an evolutionary mismatch disorder that arises from an interaction between genetic and environmental factors [ 1 , 2 ].…”

“…Although a wide variety of theories have been proposed to explain the pathogenesis of PCOS [ 5 , 6 , 7 , 8 , 9 , 10 ], recent evolutionary models have provided a unified framework [ 1 , 2 ]. Evolutionary models characterize PCOS as an evolutionary mismatch disorder that arises from an interaction between genetic and environmental factors [ 1 , 2 ]. Rapid cultural changes in the contemporary environment have outpaced genetic adaptation and resulted in a mismatch between modern dietary and environmental exposures and behaviors, and selective metabolic and reproductive traits [ 1 ].…”

“…Rapid cultural changes in the contemporary environment have outpaced genetic adaptation and resulted in a mismatch between modern dietary and environmental exposures and behaviors, and selective metabolic and reproductive traits [ 1 ]. As a result, adaptive physiological survival pathways that result in the activation of inflammation, variation in insulin sensitivity, preferential abdominal fat accumulation, and the downregulation of reproduction, become pathological following exposure to lifestyle and environmental factors [ 1 , 2 ]. The development of chronic systemic inflammation, IR, and hyperandrogenism predispose women with PCOS to a range of chronic diseases and pregnancy complications [ 11 , 12 , 13 , 14 , 15 ].…”

“…Polycystic ovary syndrome is a systemic metabolic and endocrine disorder that results from the disturbance of adaptive interdependent homeostatic survival networks (metabolic, immune, and neuroendocrine) [1][2][3][4]. Although a wide variety of theories have been proposed to explain the pathogenesis of PCOS [5][6][7][8][9][10], recent evolutionary models have provided a unified framework [1,2]. Evolutionary models characterize PCOS as an evolutionary mismatch disorder that arises from an interaction between genetic and environmental factors [1,2].…”