Heat Shock Proteins in Sperm Capacitation: A Functional Perspective Publisher



Mihanfar A ; Mutsher M K ; Shams F ; Amani A M ; Ghasemzadeh N ; Rahnama M ; Golchin A
Source: Tissue and Cell Published:2027

Abstract

Spermatozoa undergo capacitation in the female reproductive tract to acquire competence to fertilize the oocyte. Studies describing the molecular pathways underlying successful fertilization indicate that the oviduct regulates the contact between sperm and oocyte. Among these pathways, heat shock proteins (HSPs) are recognized as critical regulators of sperm capacitation. This study synthesizes current understanding of the functional roles of HSPs in sperm capacitation, specifically examining their involvement in protein folding, chaperone activity, signal transduction, and the formation of critical protein complexes, thereby evaluating their potential as targets for future investigations into male infertility. Although, specific interactions of HSPs have been identified, further research is necessary to clarify the roles of these complexes in sperm function. This review presents current knowledge of how HSPs and other signaling molecules affect intracellular signaling pathways during sperm capacitation. Proteomics and metabolomics studies have shown that HSPs are differentially expressed in various male infertility disorders; however, further reviews and extensive clinical trials are necessary to corroborate these findings and confirm HSPs as reliable biomarkers for routine clinical application. Innovative technologies and research methodologies continue to emerge, including CRISPR/Cas9 gene editing, flow cytometry for dynamic processes, high-resolution protein interactions, and advanced proteomic analyses, which may improve our understanding of the impact of HSPs on male infertility. Understanding the specific mechanisms by which HSPs influence sperm capacitation may facilitate the development of new infertility treatments. Further inquiry into the role of HSPs in sperm motility holds significant promise to enhance understanding of male fertility and develop novel strategies for infertility therapy. © 2026 Elsevier Ltd