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Recently, Bódis et al. simultaneously examined serum and follicular fluid levels of SIRT1 and SIRT6 in healthy women with normal body weight and several years of fertility problems, who had undergone in vitro fertilization, whether it resulted in a successful pregnancy or not. It has a known role in the pathogenesis of type 2 diabetes, obesity, cardiovascular disease, inflammation and arthritis, osteoporosis, neurodegenerative diseases, and cancer as well as aging and fragility 22,23,24. The best known and described role of SIRT1, which is present in the liver, skeletal muscle, adipose tissue, pancreas, and brain, is its participation in the regulation of glucose and lipid metabolism, insulin secretion, energy intake, oxidative balance regulation, and immune system action.
The NAD+ binding region is made up of a core six-stranded parallel β sheet with strands β1-3 and β7-9, as well as eight helices namely, αA, αB, αG, αH, and αJ-M, that pack against the β sheet core. The Rossmann fold is a three-layered sandwich like structure made up of alternating beta strands and alpha helical segments found in proteins that bind nucleotides. The catalytic core of SIRT1 is made up of 277 amino acid residues and has one small and one large sub-domain. The catalytic domain ranges from amino acid residues 234 to 510 and the C-terminal regulatory section ranges from amino acid residues 641 to 665. Various in vivo experimental data suggests that, activity like deacetylation of histones cause recombination suppression, silencing, and life extension.
SIRT6 is a nuclear protein having both deacetylase and ADP-ribosyltransferase activity.17,46 Recently SIRT6 was shown to be able to remove long-chain fatty acyl group from lysine to regulate tumor necrosis factors (TNF)-α secretion.47 SIRT6 has been implicated in the regulation of transcription, genome stability, metabolism, and lifespan. SIRT1 is primarily a nuclear deacetylase.21 It contains at least two nuclear localization signals and two nuclear export signals, and can shuttle between the nucleus and cytoplasm under certain conditions.22 SIRT1 removes the acetyl group from the ɛ-amino group of lysine residues in histones and non-histone proteins, and regulates target gene expression and protein activities that control various cellular processes such as cell proliferation, differentiation, apoptosis, metabolism, DNA damage and stress response, genome stability, and cell survival in complex matters (Table 1). Sirtuins are also known as class III histone deacetylases (HDACs), and their unique NAD+-dependency distinguishes sirtuins from other (classes I, II, and IV) HDACs.
Authors concluded that perturbations caused by SIRT3 via post-translational protein modification in human granulosa and cumulus cells may be a causative factor in the decline of oocyte viability in women with reduced ovarian reserve and advanced maternal age. The action of this deacetylase on glutamate GDH has been confirmed in granulosa cells obtained from young healthy women by subjecting them to resveratrol and nicotinamide action (as known sirtuins activator and inhibitor, respectively). They also found that only SIRT3 mRNA expression is altered by RSV, but SIRT1, 3 and 5 overexpression did not result in a change in the steroid profile of H295R cells, which suggests that resveratrol may not significantly engage sirtuins to modulate steroid production. The authors reported that cisplatin, accompanied with ABT737, promoted apoptosis and decreased the mitochondrial membrane potential of ovarian cancer cells.
Sirtuins regulate important physiological events, including aging and cell metabolism, mainly by protecting cells and tissues from oxidative damage. Additionally, physiological levels of reactive oxygen species (ROS) have a pivotal role in the female reproductive system during folliculogenesis and oocyte maturation and may also affect the outcomes of assisted reproductive technology (ART) . ART—assisted reproductive technology; DNA—deoxyribonucleic acid; GCs—granulosa cells; IVM-MII—in vitro matured metaphase II oocytes; mRNA—messenger RNA; miRNA—microRNA; OS—oxidative stress; RIF—recurrent implantation failure; ROS—reactive oxygen species. The authors suggest that the observed elevated SIRT1 levels may result from inflammation imbalance and oxidative stress in RIF patients . Additionally, in RIF patients, they revealed higher levels of this deacetylase than in non-pregnant women and healthy pregnant women, but the observed differences did not reach statistical significance.
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