Abstract
The epigenetic mechanisms controlling germ cell development and differentiation are still not well understood. Sirtuin-1 (SIRT1) is a nicotinamide adenosine dinucleotide (NAD)-dependent histone deacetylase and belongs to the sirtuin family of deacetylases. It catalyzes the removal of acetyl groups from a number of protein substrates. Some studies reported a role of SIRT1 in the central and peripheral regulation of reproduction in various non-primate species. However, testicular SIRT1 expression and its possible role in the testis have not been analyzed in primates. Here, we document expression of SIRT1 in testes of different primates and some non-primate species. SIRT1 is expressed mainly in the cells of seminiferous tubules, particularly in germ cells. The majority of SIRT1-positive germ cells were in the meiotic and postmeiotic phase of differentiation. However, SIRT1 expression was also observed in selected premeiotic germ cells, i.e., spermatogonia. SIRT1 co-localized in spermatogonia with irisin, an endocrine factor specifically expressed in primate spermatogonia. In marmoset testicular explant cultures, SIRT1 transcript levels are upregulated by the addition of irisin as compared to untreated controls explants. Rhesus macaques are seasonal breeders with high testicular activity in winter and low testicular activity in summer. Of note, SIRT1 mRNA and SIRT1 protein expression are changed between nonbreeding (low spermatogenesis) and breeding (high spermatogenesis) season. Our data suggest that SIRT1 is a relevant factor for the regulation of spermatogenesis in primates. Further mechanistic studies are required to better understand the role of SIRT1 during spermatogenesis.
Highlights
Accepted: 17 March 2021Germ cell function is substantially regulated by epigenetic mechanisms including histone modifications [1,2,3]
Recent studies have demonstrated a role of SIRT1 deacetylase in central and peripheral regulation of reproduction in various non-primate models [16,17]
SIRT1 was co-localized in some spermatogonia with irisin, an endocrine factor expressed in primate spermatogonia [20]
Summary
Accepted: 17 March 2021Germ cell function is substantially regulated by epigenetic mechanisms including histone modifications [1,2,3]. Histone structure is modified by methylation, phosphorylation, ubiquitination, and acetylation of lysine and serine residues in histone tails of the nucleosome [4]. An acetyl group is added to histone tails at lysine residues. Histone acetylation reduces the electrostatic affinity between DNA and histones, resulting in a transcriptionally active euchromatin state of genomic DNA that promotes binding of transcription factors. HATs, which comprise the Gcn5/PCAF, p300/CBP, and MYST subfamilies [7], enhance transcription activities in cells by augmenting acetylation of histone lysine residues. Acetyl groups of histone lysine residues are removed by HDACs, which results in a more compact heterochromatin state limiting binding of transcription factors and attenuating transcription [5]
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