SIRT1: A Key Player in Male Reproduction

Abstract

Reproduction is the way to immortality for an individual, and it is essential to the continuation of the species. Sirtuins are involved in cellular homeostasis, energy metabolism, apoptosis, age-related problems, and sexual reproduction. Sirtuin 1 (SIRT1) belongs to the sirtuin family of deacetylases, and it is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase. It removes the acetyl group from a variety of substrates. SIRT1 regulates endocrine/metabolic, reproductive, and placental development by deacetylating histone, different transcription factors, and signal transduction molecules in a variety of cellular processes. It also plays a very important role in the synthesis and secretion of sex hormones via regulating the hypothalamus-pituitary-gonadal (HPG) axis. Moreover, SIRT1 participates in several key stages of spermatogenesis and sperm maturation. The current review will give a thorough overview of SIRT1’s functions in male reproductive processes, thus paving the way for more research on restorative techniques and their uses in reproductive medicine.

Functional role of autophagy in testicular and ovarian steroidogenesis

“…These findings indicate that the autophagy-lysosome pathway breaks down the Na + /H + exchanger regulatory factor 2 (NHERF2), which functions as a suppressor of SR-BI. Consequently, the accumulation of NHERF2 leads to the suppression of SR-BI when ATG5, ATG7, and Sirt1 are deleted in murine Leydig cells, resulting in compromised cholesterol absorption and decreased testosterone production as depicted in Figure 3B (Gao et al, 2018a;Khawar et al, 2021b;Khawar et al, 2022). Mechanistic depiction of autophagy.…”

“…Earlier, we have discussed autophagy in relation to lipolysis (Khawar et al, 2019;Khawar et al, 2021a) in the liver (Nazeer et al, 2023) and reproduction (Gao et al, 2019;Gao et al, 2020;Khawar et al, 2022). Interestingly, extensive research on autophagy in normative and pathological endocrine settings has yielded promising knowledge, whereby a unified understanding of steroidogenesis in reproductive organs remains enigmatic.…”

Role of SIRT1 in Chemoresistant Leukemia

“…Among the different isoforms, SIRT1 is the most studied, most likely due to its involvement in the homeostatic regulation of different organs and tissues, both in the adult stage and during embryonic development [26]. Although it was originally associated with longevity [11,27,28], it plays a role in regulating metabolism as well as in DNA repair in the inflammatory and stress response [29][30][31].…”

Reduced SIRT1 and SIRT3 and Lower Antioxidant Capacity of Seminal Plasma Is Associated with Shorter Sperm Telomere Length in Oligospermic Men

“…Sirtuins, particularly SIRT1 and SIRT3, are highly expressed in mammalian testicular tissue, probably because spermatogenesis depends on glycolysis and the generation of ATP by pyruvate metabolism in mitochondria [14][15][16]. Immuno-blotting positive staining in late spermatogonia, spermatocytes, round spermatids and pachytene spermatocytes indicates that SIRT1 is a nuclear protein, and it plays an important role in the development of germ cells during spermatogenesis [17,18]. A gene ontology study in Sirt1 −/ − mice has provided further evidence that many genes involved in spermatogenesis are differentially expressed in testis, leading to the suggestion that SIRT1 deficiency influences fertility by regulating the transcription of several spermatogenic genes [15,17].…”