The NLRP3 inflammasome: molecular activation and regulation in spermatogenesis and male infertility; a systematic review

Abstract

Abstract Background Infertility related to varicocele, infections, metabolic dysfunctions, oxidative stress and environmental toxicants is also associated with inflammatory processes that ultimately lead to the activation of the inflammasome pathway (IP). IP is classically activated by DAMPs, MAMPs or LAMPs, which stand for Damage-, Microbe- or Lifestyle-Associated Molecular Patterns, respectively. The most important player in IP activation is the NLRP3 (NOD[Nuclear oligomerization domain]-, LRR[Leucine rich repeat]- and pyrin domain-containing protein 3) which functions as an intracellular sensor of D/M/L-AMPs resulting in activation of caspase-1, promotion of apoptosis, pyroptosis and generation of inflammatory cytokines. This review addresses the question of whether IP activation might be associated with male infertility situations. Results & conclusions We conducted a systematic review of articles published in the Google Scholar, and PubMed databases through October 2021. It turns out that inflammasome activation and its consequences including cytokine storms, apoptosis and pyroptosis could be associated with the reduced sperm count as well as the structural and functional sperm defects recorded in several situations associated with male infertility suggesting that anti-inflammatory therapeutic strategies could be possibly considered to restore male fertility in future research.