Hypoxia enhances autophagy level of human sperms

This study investigated the connection between oxygen sensing and autophagy in human sperm. Healthy semen and semen from men with asthenozoospermia were treated with hypoxia-inducible factor-1α (HIF-1α) interferents, specifically lificiguat (YC-1) and cobalt chloride (CoCl2). Label-free quantitative proteomic technology was employed to identify differentially expressed proteins in human semen under hypoxic conditions, with selected proteins detected using ELISA.

Results showed that autophagy levels in sperm increased in both the YC-1 + healthy group and the CoCl2 + astheno group, while sperm vitality decreased. A total of 17, 34, and 35 differentially expressed proteins were identified in the astheno group, the YC-1 + healthy group, and the CoCl2 + astheno group, respectively. These proteins were primarily linked to processes such as protein processing in the endoplasmic reticulum, Th17 cell differentiation, progesterone-mediated oocyte maturation, glycolysis/gluconeogenesis, the HIF-1 signaling pathway, amino acid biosynthesis, and carbon metabolism.

Notably, the expression levels of proteins HIF-1α, LC3B, histone H4, cathepsin L, and ENO1 showed significant changes across the groups. The findings suggest that hypoxia can elevate sperm autophagy levels while reducing their vitality, primarily through the HIF-1 and glycolysis/gluconeogenesis signaling pathways. Additionally, proteins histone H4, cathepsin L, glutathione synthetase, and ENO1 are proposed as potential biomarkers for autophagy and vitality in sperm with asthenozoospermia.