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Int. J. Mol. Sci. 2015, 16(5), 9831-9849;

Abnormal Mitochondrial Function and Impaired Granulosa Cell Differentiation in Androgen Receptor Knockout Mice

Graduate Institute of Clinical Medicine & Department of Obstetrics and Gynecology, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
Department of Biochemistry and Molecular Cell Biology, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
Center of General Education, Chang Gung University, Taoyuan 333, Taiwan
George H. Whipple Lab for Cancer Research, Departments of Pathology, Urology and Radiation Oncology, University of Rochester Medical Center, Rochester, NY 14642, USA
Authors to whom correspondence should be addressed.
Academic Editors: Jaime M. Ross and Giuseppe Coppotelli
Received: 31 January 2015 / Revised: 20 April 2015 / Accepted: 22 April 2015 / Published: 30 April 2015
(This article belongs to the Special Issue Mitochondrial Dysfunction in Ageing and Diseases)
Full-Text   |   PDF [1892 KB, uploaded 30 April 2015]   |  


In the ovary, the paracrine interactions between the oocyte and surrounded granulosa cells are critical for optimal oocyte quality and embryonic development. Mice lacking the androgen receptor (AR−/−) were noted to have reduced fertility with abnormal ovarian function that might involve the promotion of preantral follicle growth and prevention of follicular atresia. However, the detailed mechanism of how AR in granulosa cells exerts its effects on oocyte quality is poorly understood. Comparing in vitro maturation rate of oocytes, we found oocytes collected from AR−/− mice have a significantly poor maturating rate with 60% reached metaphase II and 30% remained in germinal vesicle breakdown stage, whereas 95% of wild-type AR (AR+/+) oocytes had reached metaphase II. Interestingly, we found these AR−/− female mice also had an increased frequency of morphological alterations in the mitochondria of granulosa cells with reduced ATP generation (0.18 ± 0.02 vs. 0.29 ± 0.02 µM/mg protein; p < 0.05) and aberrant mitochondrial biogenesis. Mechanism dissection found loss of AR led to a significant decrease in the expression of peroxisome proliferator-activated receptor γ (PPARγ) co-activator 1-β (PGC1-β) and its sequential downstream genes, nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), in controlling mitochondrial biogenesis. These results indicate that AR may contribute to maintain oocyte quality and fertility via controlling the signals of PGC1-β-mediated mitochondrial biogenesis in granulosa cells. View Full-Text
Keywords: androgen receptor; granulosa cell; PGC1-β; mitochondria androgen receptor; granulosa cell; PGC1-β; mitochondria

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Wang, R.-S.; Chang, H.-Y.; Kao, S.-H.; Kao, C.-H.; Wu, Y.-C.; Yeh, S.; Tzeng, C.-R.; Chang, C. Abnormal Mitochondrial Function and Impaired Granulosa Cell Differentiation in Androgen Receptor Knockout Mice. Int. J. Mol. Sci. 2015, 16, 9831-9849.

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