Male SIRT1 insufficiency leads to sperm with decreased ability to hyperactivate and fertilize

Abstract

Sperm physiology is mainly affected by the functions of testis and, during spermatogenesis, sperm are provided of proteins driving posterior motility (Björkgren & Sipilä, 2019). For example, NAD +dependent histone deacetylases (Sirtuins) need to be expressed in testes for proper sperm motility (Coussens et al., 2008). Moreover, spermatozoa are transcriptionally and translationally silent, therefore the ability to acquire fertilization competence, i.e. support capacitation and hyperactivation, depends on the proteins already synthesized during spermatogenesis. Interestingly, aging results in decreased sirtuin 1 (SIRT1) expression in testes (Grabowska et al., 2017) and defective basal sperm motility (prior to capacitation). However, whether this SIRT1 insufficiency affects posterior sperm ability to hyperactivate deserves to be studied. To test this possibility, we compared the dynamics of motility-based sperm subpopulations during capacitation and fertilization ability of Sirt1 +/− mutant males and wild-type (WT) siblings. Our study support that (I) SIRT1 contributes sperm to go through hyperactivation and (II) Sirt1 +/− mice as good model to identify molecular factors developing the age-related sub-/infertility. | ME THODS | AnimalsFourteen to 18-week-old males of germ-line Sirt1 +/− (n = 3) and their WT (Sirt1 +/+ ) siblings (n = 3) were used. Sirt1 +/− genotype is based on the excision of exons 5, 6 and 7 of Sirt1 allele. Animal procedures were done in accordance with the ActNo.246/1992 of the Animal Welfare Advisory Committee (Czech Republic).

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

“…SIRT1 and SIRT3 proteins are found in seminal plasma, and their levels in seminal plasma are inversely correlated with oxidative stress biomarkers and the amount of sperm DNA fragmentation, as evident in our study. These findings are in agreement with the previously published reports [31,32,104,105]. Seminal plasma provides nutrients for the maintenance of the maturing sperms, and the increased generation of ROS could result in reduced sperm metabolism and diminish motility, thus leading to infertility [106,107].…”

The sirtuin family in health and disease

“… 876 In addition, to investigate SIRT1 regarding adjuvant strategies in the treatment of male infertility, dysregulation of SIRT1 and mitochondrial SIRT (SIRT3-5) genes were associated with human male infertility. 921 , 922 In female genital system disease, a limited number of studies have paid attention to polycystic ovary syndrome (PCOS) and endometriosis. PCOS patients had higher SIRT1 levels than healthy controls 923 and involvement of the SIRT1/AMPK axis in autophagy activation in PCOS.…”

Resveratrol Improves the Frozen-Thawed Ram Sperm Quality

“…The findings of previous research have demonstrated that SIRT1 reduction leads to mitochondrial dysfunction by increasing ROS, LPO, and DNA damage in sperm, resulting in decreased sperm fertilization ability [48]. Similarly, studies by Cuerda et al have shown that insufficient SIRT1 function in men leads to overactivation of sperm and decreased fertilization ability [49]. Thus, SIRT1 expression was significantly positively correlated with sperm concentration, total motility, and normal sperm morphology.…”