Hyperandrogenemia alters mitochondrial structure and function in the oocytes of obese mouse with polycystic ovary syndrome

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Authors:

Neil R. Chappell, M.D., Beth Zhou, M.D., Pardis Hosseinzadeh, M.D., Amy Schutt, M.D., William E. Gibbons, M.D., Chellakkan S. Blesson, Ph.D. 

Abstract:

Background

Hyperandrogenemia in an obese polycystic ovary syndrome (PCOS) mouse model results in altered glucose/insulin metabolism and mitochondrial structure and function in the oocytes, in part explaining adverse outcomes and inheritance patterns seen in PCOS.


Objective

To study the oocyte quality by means of mitochondrial structure and function in a well-established classic PCOS mouse model.


Design

Animal study using an obese PCOS mouse model compared with control.


Setting

Animal research facility in a tertiary care university hospital setting.


Animals

C57/B6J mice.


Intervention(s)

Three-week-old mice had subdermal implants of dihydrotestosterone controlled release pellet or placebo for 90 days.


Main Outcome Measure(s)

The mouse model was validated by performing glucose tolerance test and glycated hemoglobin level, body weight, and estrous cycle analyses. Oocytes were subsequently isolated and were used to investigate mitochondrial membrane potential, oxidative stress, lipid peroxidation, adenosine triphosphate production, mitochondrial DNA copy number, transcript abundance, histology, and mitochondrial ultrastructure.


Result(s)

Results showed glucose intolerance and hyperinsulinemia along with dysregulated estrus cycle. Analysis of the oocytes indicated impaired inner mitochondrial membrane function, increased adenosine triphosphate production and mitochondrial DNA copy number, altered RNA transcript abundance, and aberrant ovarian histology. Electron microscopy of the oocytes revealed severely impaired mitochondrial ultrastructure.


Conclusion(s)

The obese PCOS mouse model shows a decreased oocyte quality related to impaired mitochondrial function.

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.