Mechanisms of Male Reproductive Impairment During High-Altitude Hypoxic Exposure

The detrimental effects of high-altitude hypoxia on male reproductive health have garnered increasing research attention. However, the relationship between exposure duration and the extent of reproductive system impairment remains to be fully elucidated. In this study, we developed animal models replicating reproductive damage in male rats under both acute and chronic high-altitude hypoxic conditions. Through integrated bioinformatics analysis and experimental validation, we systematically identified key molecular pathways and core gene regulatory networks involved in hypoxia-induced reproductive dysfunction, while also evaluating their translational relevance to human health. Our findings demonstrate that high-altitude exposure substantially impaired spermatogenic quality; disrupted reproductive hormone homeostasis; triggered testicular oxidative stress and inflammatory responses; and compromised tissue architecture integrity. Further investigation through protein-protein interaction and KEGG pathway analyses revealed that high-altitude hypoxia markedly downregulated Pcdhb1 and Lrp6 gene expression, resulting in aberrant activation of the Wnt signaling pathway and consequent deleterious impacts on male reproductive function under both acute and chronic hypoxic conditions.