131. SIRT3 IN OVARIAN CELLS IS ALTERED BY MATERNAL AGE AND OVARIAN RESERVE
L. Pacella A , D. Zander-Fox A B , T. Hussein A B , T. Fullston A and M. Lane A BA Obstetrics and Gynaecology, Adelaide University, Adelaide, SA, Australia.
B Embryology, Repromed, Dulwich, SA, Australia.
Reproduction, Fertility and Development 22(9) 49-49 https://doi.org/10.1071/SRB10Abs131
Published: 6 September 2010
Abstract
Maternal age and reduced AMH levels affect the follicular environment and consequently oocyte viability. The Sirtuin family of protein deacetylases are able to regulate various cellular functions involved in the ageing process in other tissues. In particular, SIRT3 is related to longevity in several cell types and regulates mitochondrial function, however, its presence and role in ovarian cells remains unknown. This study therefore, investigated the presence of SIRT3 in granulosa and cumulus cells, from patients undergoing IVF, and determined the impact of maternal age and low AMH on SIRT3 levels. Granulosa and cumulus cells were collected from women (n = 36), after informed consent, and classified into 3 groups; A (<35 years, normal AMH), B (>40 years (advanced maternal age), normal AMH) and C (<35 years, low AMH). The presence of SIRT3 was determined by q-PCR (expressed as fold-change) or immunohistochemistry. SIRT3 was present in the ovarian cells of all patients analysed. SIRT3 gene expression was reduced in granulosa cells from women with low AMH (0.67 ± 0.17) compared to women with normal AMH (1.00 ± 0.23; P < 0.05). In cumulus cells, levels were reduced with advanced maternal age (0.81 ± 0.08) compared to women <35 years (1.00 ± 0.22; P < 0.05). SIRT3 protein co-localised with mitochondria in the ovarian cells, confirming previous findings for other cell types. In comparison to women <35 years with normal AMH, image analysis determined that SIRT3 protein levels were significantly reduced in the granulosa and cumulus cells from women of advanced maternal age by 21.4% and 31.8% and in women with low AMH by 34.1% and 47.2% respectively. This is the first study to demonstrate SIRT3 presence in human ovarian cells. The observation that SIRT3 levels are altered by advanced maternal age or low AMH (reduced ovarian reserve) implicate its role in ovarian ageing and plausibly in the decrease in oocyte viability observed in these women.
