Heat Shock Protein Mechanisms in Male Fertility

Heat shock proteins (HSPs) constitute a conserved family of molecular chaperones that safeguard protein integrity under stress and regulate key stages of male reproductive physiology. In the testis, HSP70 and HSP90 subfamilies ensure correct folding of nascent polypeptides, protect germ cells from apoptosis, and maintain normal progression of spermatogenesis. During epididymal maturation and ejaculation, HSPs modulate sperm membrane stability, intracellular calcium homeostasis and reactive oxygen species balance, thereby preserving motility and genomic integrity. In the female tract, HSP-mediated control of capacitation-associated protein tyrosine phosphorylation and acrosome reaction underlies successful zona penetration and gamete fusion. Beyond their intracellular roles, several HSP isoforms are present on the sperm surface where they participate in sperm–egg recognition. In agricultural and clinical contexts, variations in HSP expression correlate with subfertility, rendering them attractive biomarkers for semen quality assessment, cryopreservation resilience and targeted therapeutic intervention. Elucidation of HSP networks has broad implications for understanding idiopathic male infertility, improving livestock breeding efficiency and refining assisted-reproductive techniques worldwide.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Heat Shock Protein Mechanisms in Male Fertility publication trend

The graph below shows the total number of articles in heat shock protein mechanisms in male fertility across all publications each year (not limited to Nature Index journals).

Technical terms

Heat shock protein (HSP): A class of highly conserved chaperone proteins induced by cellular stress that assist in protein folding, prevent aggregation and regulate intracellular signalling.

Chaperone protein: A molecule that binds nascent or misfolded proteins to facilitate correct folding and prevent degradation or aggregation.

Capacitation: A post-ejaculatory maturation process in the female reproductive tract whereby sperm acquire fertilising capability through membrane and biochemical changes.

Acrosome reaction: A calcium-dependent exocytotic event in capacitated sperm that releases enzymes to penetrate the oocyte’s zona pellucida.

Oxidative stress: An imbalance between reactive oxygen species production and antioxidant defences that can damage lipids, proteins and DNA in sperm cells.

References

1. Heat Shock Protein 90 Has Roles in Intracellular Calcium Homeostasis, Protein Tyrosine Phosphorylation Regulation, and Progesterone-Responsive Sperm Function in Human Sperm. PLOS ONE (2014).
2. Implications of sperm heat shock protein 70-2 in bull fertility. Veterinary World (2022).
3. Identification of HSP70-2 and PRM-1 mRNA, proteins, and analyses of their association with fertility using frozen-thawed sperm in Madura bulls. Animal Bioscience (2023).
4. Bovine sperm HSP-70 molecules: a potential cryo-tolerance marker associated with semen quality and fertility rate. Frontiers in Veterinary Science (2023).