Objective: To investigate the specific mechanism of hypoxia-inducible factor 1 alpha (HIF-1α) in the regulation of human sperm apoptosis, and to provide a new theoretical reference and scientific basis for the diagnosis and treatment of asthenospermia and other related conditions. Methods: Semen samples were categorized into the normal group and asthenospermia group based on sperm motility criteria. HIF-1α interfering agent cobalt chloride (CoCl2) and guanylate cyclase activator (Lificiguat, YC-1) were added respectively, with a control group established accordingly. Sperm motility (using anterior viability rate as an index), apoptosis level, ATP level, mitochondrial membrane potential, and reactive oxygen species (ROS) level were measured. The expression levels of HIF-1α, p-PI3K, and Bcl-2 in the samples were analyzed using Western blotting. Results: Following CoCl2 treatment, there was a significant increase in sperm apoptosis compared to the normal control group (12.51% ± 2.50% VS 11.15% ± 2.42%); additionally, sperm motility (45.34% ± 3.37% VS 51.36% ± 11.68%), ATP production (11.51 ± 2.87 nM/μL VS 14.99 ± 2.83 nM/μL), ROS levels, and mitochondrial membrane potential all decreased significantly (all P < 0.05). Furthermore, the expression levels of HIF-1α and p-PI3K increased significantly while Bcl-2 expression decreased (all P < 0.05). Conversely, following YC-1 treatment there was a significant decrease in sperm apoptosis compared to the asthenospermia control group (8.59% ± 2.86% VS 9.37% ± 3.07%); along with this change came significant increases in sperm motility (38.51% ± 5.56% VS 21.86% ± 16.43%), ATP production (13.13 ± 4.01 nM/μL VS 11.05 ± 3.67 nM/μL) and ROS levels, decrease in mitochondrial membrane potential levels (all P < 0.05). Moreover, compared with the control group, the expression levels of p-PI3K and HIF-1α in the YC-1 treatment group were decreased, and the expression level of Bcl-2 was increased (all P < 0.05). Conclusion: HIF-lα can influence human sperm apoptosis and motility through the PI3K signaling pathway.
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