Human umbilical cord mesenchymal stem cell transplantation protects against reproductive damage induced by high-altitude hypoxia exposure in male mice

Cui Shuo; Li Xiujuan; Wang Wenting; Yang Lihong; He Sheng; Lei Lijian; Xie Jun

doi:10.12307/2026.676

Abstract：BACKGROUND:High-altitude hypoxia has been reported to damage the male reproductive system,but whether stem cells can protect against male reproductive damage caused by high-altitude hypoxia has not been reported. OBJECTIVE:To investigate the preventive effect of human umbilical cord mesenchymal stem cell transplantation on reproductive damage in hypoxia-exposed male mice. METHODS:Human umbilical cord mesenchymal stem cells were isolated and cultured to identify the three-lineage differentiation and specific phenotype markers.Totally 21 C57BL/6 male mice were randomly divided into control,hypoxia,and stem cell groups(n=7).A mouse model of chronic-intermittent hypoxia was established to simulate hypoxia exposure at an altitude of 5 000 m(11.1%oxygen volume fraction)in the hypoxia and stem cell groups.On the last day of each week of hypoxia exposure,mice in the stem cell group were injected with 1×106 human umbilical cord mesenchymal stem cells through the tail vein once a week for a total of 6 injections,while the other groups were injected with PBS.Mouse body weight,food and water intake were monitored during the experiment.After the end of hypoxia exposure,the testes were analyzed for morphology,ultrastructure,reactive oxygen species level and mitochondrial membrane potential.The epididymal tissues were analyzed for hematoxylin-eosin staining and sperm motility.The homing ability of the stem cells was observed by DIL tracer method. RESULTS AND CONCLUSION:(1)Human umbilical cord mesenchymal stem cell transplantation significantly improved water and food intake in hypoxic mice,but had no significant effect on body weight.(2)Morphological analysis revealed that hypoxia induced edema in the testes and epididymides of mice,accompanied by the shedding of spermatogenic cells.In contrast,human umbilical cord mesenchymal stem cell transplantation alleviated the structural damage caused by hypoxia exposure and the swelling and atrophy of germ cell mitochondria.Additionally,human umbilical cord mesenchymal stem cell transplantation significantly reduced the reactive oxygen species levels induced by hypoxia exposure,restored the mitochondrial membrane potential,and enhanced sperm motility in hypoxic mice.(3)Tracer experiments indicated that human umbilical cord mesenchymal stem cells,after being injected into mice through the tail vein,mainly accumulated in the lung tissue and had a lower homing capacity in the testis.In conclusion,human umbilical cord mesenchymal stem cell transplantation effectively protected the mitochondrial structure and function of germ cells,alleviated testicular and epididymal edema caused by hypoxia,and thus restored spermatogenesis and sperm motility in mice.