Abstract

Hormonal disturbances, such as hyperandrogenism, are considered important for developing polycystic ovary syndrome (PCOS) in humans. Accordingly, directly hormone-regulated animal models are widely used for studying PCOS, as they replicate several key PCOS features. However, the pathogenesis and treatment of PCOS are still unclear. In this review, we aimed to investigate animal PCOS models and PCOS-like phenotypes in animal experiments without direct hormonal interventions and determine the underlying mechanisms for a better understanding of PCOS. We summarized animal PCOS models that used indirect hormonal interventions and suggested or discussed pathogenesis of PCOS-like features in animals and PCOS-like phenotypes generated in other animals. We presented integrated physiological insights and shared cellular pathways underlying the pathogenesis of PCOS in reviewed animal models. Our review indicates that the hormonal and metabolic changes could be due to molecular dysregulations, such as upregulated PI3K-Akt and extracellular signal-regulated kinase (ERK) signalling, that potentially cause PCOS-like phenotypes in the animal models. This review will be helpful for considering alternative animal PCOS models to determine the cellular/molecular mechanisms underlying PCOS symptoms. The efforts to determine the specific cellular mechanisms of PCOS will contribute to novel treatments and control methods for this complex syndrome.

Highlights

  • Various animal models have been developed and studied for the human polycystic ovary syndrome (PCOS) for more than 60 years

  • We have briefly summarized naturally developed PCO and relevant mechanisms in other animals to search for shared pathophysiology with respect to polycystic ovarian morphology, hormonal alteration, and accompanying metabolic syndromes

  • We aimed to introduce mainly indirect hormonal methods for developing PCOS-like phenotypes in animals; we have provided a short description of hormone-induced animal PCOS models

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Summary

Introduction

Various animal models have been developed and studied for the human polycystic ovary syndrome (PCOS) for more than 60 years. A huge gap exists between humans and laboratory animals, which are mainly rodents, with respect to their reproductive physiology (e.g., differences in ovulation number and patterns, released hormone profile, sensitivity to hormones, behavioural styles, and anatomy of the organs), studies using animal models are essential to explore the pathophysiology of PCOS in vivo. According to Rotterdam’s criteria for PCOS diagnosis [1], the key features of PCOS that should be manifested in the animal models are hyperandrogenism, too many antral follicles and abnormal estrous cycle (amenorrhea or oligomenorrhea in case of non-human primates). Laboratory rodents, unlike humans, do not develop PCOS-like phenotypes naturally, the persistence of ovarian follicles with a prolonged estrous period has been reported in natural housed rats [2].

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