Abstract
Silent information Regulators (SIRT1) gene stimulates antioxidants’ expression, repairs cells damaged by oxidative stress (OS), and prevents the cells’ dysfunction. In particular, the role of different Sirtuins, particularly SIRT1 in reproduction, has been widely studied over the past decade. Decreased SIRT 1 causes mitochondrial dysfunction by increasing Reactive Oxygen Species (ROS), lipid peroxidation, and DNA damage in both male and female gametes (Sperms and Oocytes), leading to infertility. In the female reproductive system, SIRT1 regulates proliferation and apoptosis in granulosa cells (GCs), and its down-regulation is associated with a reduced ovarian reserve. SIRT1 also modulates the stress response to OS in GCs by targeting a transcription factor vital for ovarian functions and maintenance.ROS-mediated damage to spermatozoa’s motility and morphology is responsible for 30–80% of men’s infertility cases. High levels of ROS can cause damage to deoxyribo nucleic acid (DNA) in the nucleus and mitochondria, lipid peroxidation, apoptosis, inactivation of enzymes, and oxidation of proteins in spermatozoa. SIRT 1 is a cardioprotective molecule that prevents atherosclerosis by modulating various mechanisms such as endothelial injury due to impaired nitric oxide (NO) production, inflammation, OS, and regulation of autophagy. SIRT 1 is abundantly expressed in tubular cells and podocytes. It is also found to be highly expressed in aquaporin 2 positive cells in the distal nephron suggesting its involvement in sodium and water handling. SIRT1 improves insulin resistance by reducing OS and regulating mitochondrial biogenesis and function. It also decreases adiposity and lipogenesis and increases fatty acid oxidation. So, its involvement in the multiple pathways ensures its unique role in reproductive and metabolic derangement mechanisms.
Highlights
Sirtuins (NAD dependant-deacylase) are involved in the deacetylation of histones and transcriptional factors regulating the cell cycle, resistance to oxidative stress, and metabolism
This review aims to gather information about crosstalk between SIRT1 and oxidative stress (OS), reproductive and metabolic functions (Table 1, Fig. 1)
In the female reproductive system, SIRT1 regulates proliferation and apoptosis in granulosa cells (GCs), especially during the follicular atretic phase, and its down-regulation is associated with a reduced ovarian reserve (Tatone et al, 2018a)
Summary
Sirtuins (NAD dependant-deacylase) are involved in the deacetylation of histones and transcriptional factors regulating the cell cycle, resistance to oxidative stress, and metabolism. They are located in all essential parts of the cell, including the nucleus, cytoplasm, and mitochondria (Morris, 2013; Merksamer et al, 2013). SIRT1 has been called the “sensor” and “guardian of the redox state” in granulosa cells and oocytes(3). A vast range of cellular activities is controlled by SIRT1, including programmed cell death, autophagy, cell migration, and differentiation. This review aims to gather information about crosstalk between SIRT1 and OS, reproductive and metabolic functions (Table 1, Fig. 1)
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