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Environmental hypoxia exposure causes fertility problems in human and animals. Compelling evidence suggests that chronic hypoxia impairs spermatogenesis and reduces sperm motility. However, it is unclear whether paternal hypoxic exposure affects fertilization and early embryo development. In the present study, we exposed male mice to high altitude (3200 m above sea level) for 7 or 60 days to evaluate the effects of hypoxia on sperm quality, zygotic DNA methylation and blastocyst formation. Compared with age-matched controls, hypoxia-treate