摘要：SummaryHUWE1 is a HECT-domain ubiquitin E3 ligase expressed in various tissues. Although HUWE1 is known to promote degradation of the tumor suppressor p53, given a growing list of its substrates,in vivofunctions of HUWE1 remain elusive. Here, we investigated the role of HUWE1 in the female reproductive system. Homozygous deletion ofHuwe1in mouse oocytes of primary follicles caused oocyte death and female infertility, whereas acute depletion of HUWE1 protein by Trim-Away technology did not impact oocytes from antral follicles. Interestingly, oocytes fromHuwe1heterozygous females matured and fertilized normally, but the majority of embryos that lacked maternalHuwe1were arrested at the morula stage after fertilization. Consequently,Huwe1heterozygous females only produced wild-type pups. Concomitant knockout ofp53did not recover fertility of theHuwe1knockout females. These findings make HUWE1 a unique and critical maternal factor indispensable for maintaining the quality of oocytes and embryos.Graphical AbstractDisplay OmittedHighlights•Oocyte-specificHuwe1KO leads to female infertility in mice•Homozygous, but not heterozygous,Huwe1KO kills oocytes before the GV stage•MaternalHuwe1is also required for preimplantation embryonic development•Defects in oocyte and embryonic development ofHuwe1KO mice are independent of p53Cell Biology; Developmental Biology
