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

Capsule Hyperandrogenemia in an obese 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 Three week old mice had subdermal implants of DHT controlled release pellet or placebo for 90 days.

Main Outcome Measures The mouse model was validated by performing glucose tolerance test, HbA1c levels, body weight and estrous cycle analyses. Oocytes were subsequently isolated and were used to investigate mitochondrial membrane potential, oxidative stress, lipid peroxidation, ATP production, mtDNA copy number, transcript abundance, histology and electron microscopy.

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

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