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HUWE1 is a HECT domain containing ubiquitin ligase implicated in neurogenesis, spermatogenesis and cancer development. The purpose of the current study is to investigate the role of HUWE1 in early embryo development. Here we demonstrate that  Huwe1  is expressed in both nucleus and cytoplasm of preimplantation mouse embryos as well as gametes. Hypoxia (5% O 2 ) treatment could significantly increase  Huwe1  expression during mouse embryo development process. HUWE1 knockdown inhibited normal embryonic development and reduced blastocyst formation, and increased apoptotic cell numbers were observed in the embryos of HUWE1 knockdown group. Human embryo staining result showed that reduced HUWE1 staining was observed in the poor-quality embryos. Furthermore, Western blot result showed that significantly reduced expression of  HUWE1  was observed in the villi of miscarriage embryos compared with the normal control, indicating that reduced expression of  HUWE1  is related to poor embryo development. Oxidative reagent, H 2 O 2  inhibited  HUWE1  expression in human sperm, indicating that  HUWE1  expression in sperm is regulated by oxidative stress. In conclusion, these results suggest that HUWE1 protein could contribute to preimplantation embryo development and dysregulated expression of  HUWE1  could be related to poor embryo development and miscarriage in IVF clinic.

HUWE1 plays important role in mouse preimplantation embryo development and the dysregulation is associated with poor embryo development in humans