Insulin Ameliorates Folliculogenesis in An Experimental Model of PCOS Mice

Document Type : Original Article


1 Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Department of Anatomical Sciences and Cognitive Neuroscience, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

4 Department of Midwifery, School of Nursing and Midwifery, Iran University of Medical Sciences, Tehran, Iran

5 Department of Anatomical Sciences, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran


Background: Insulin is an essential factor that controls female reproductive system. Insulin signaling via Foxo1 and Akt1 can improve steroidogenesis, cell proliferation, and protein synthesis. We aimed to determine the effect of insulin on possible changes in gene expression, hormonal status, and histological aspects of the ovary following the induction of the animal model of polycystic ovary syndrome (PCOS).
Materials and Methods: In this experimental study, 24 adult female NMRI mice weighing 25-30 g were randomly placed in three groups: control, PCOS (60 mg/kg dehydroepiandrosterone (DHEA) for 20 days, and PCOS+insulin (60 mg/kg DHEA for 20 days+100 μL insulin diluted in water twice a week for 30 consecutive days). Blood specimens were obtained from the heart and the serum levels of testosterone, progesterone, and estradiol were measured. Right, and left ovaries were removed for real-time polymerase chain reaction (PCR) and stereological study.
Results: DHEA injection significantly amplified the concentration of testosterone, progesterone, and estradiol. While insulin treatment amended the level of reproductive hormones. DHEA injection significantly reduced the expression levels of Irs1-4, Pdk1, Pi3k, and Akt1-3 and raised the expression level of Caspase-3. However, insulin administration amplified expression levels of Irs1-4, Pdk1, Pi3k, and Akt1-3, and reduced Caspase-3. The total volume of ovarian tissue in mice receiving DHEA significantly declined compared to the control group. Besides, a substantial decrease was detected in the number of ovarian antral, Graafian, and primordial follicles and also in the total number of corpus luteum following DHEA administration. Comparison of structural alterations in ovarian tissue between the PCOS+insulin and the PCOS groups displayed that insulin administration improved the total number of Graafian, primordial, and antral follicles and also corpus luteum.
Conclusion: In general, short-term insulin treatment showed improvement in hormonal balance, folliculogenesis, and insulin resistance in the ovaries of the PCOS mice model.


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