The Functional Relevance Of De-sumoylation Protease 7(SENP7)to Oocyte Meiosis And Embryo Development In Mouse

Human infertility nowadays has been widely recognized as a steeply increased medical and social concern facing the world,which seems to be the natural law of the rapidly development of our human society.One of the major contributors to this concern is the deterioration in the quantity and/or quality of oocytes,the germ cells of female,due to a spectrum of known and unknown factors.Deteriorated oocytes are more prone to be meiotically incompetent or chromosome missegregation during meiosis which leads to the production of aneuploid female gametes and thereby,inciting infertility,pregnancy loss and congenital defects in human.As such,deciphering the molecular mechanisms that govern mammalian oocyte meiosis and embryo development programs is of unrivaled societal and medical significance for improving human fertility.SENP7,one of the sentrin-specific proteases specialized for SUMO poly-chain editing,has been appreciated as a key mitotic regulator of heterochromatin integrity and DNA repair.However,the relevant contribution of SENP7 to the architecture of oocyte meiosis and preimplantation development in mammalian still remains elusive.We herein,by depleting the endogenous SENP7 in mouse oocytes and early embryos,dispel the myths of SENP7 in mammalian oocyte and preimplantation development.The main findings are as follow:(1)GV-stage oocytes depleted for SENP7 experience meiotic arrest at prophase I and metaphase I stages,causing substantial reduction in mature eggs production.(2)Hyperaceylation and hypomethylation of histone H3 at lysine 9 and lysine 27,and up-regulated Cdc14B/C with deteriorated CyclinB1 and CyclinB2 contribute to compromised M-phase entry(GVBD)and spindle assembly in SENP7-depleted oocytes.(3)The mislocalization of and ubiquitylation-mediated proteasomal degradation of γ-tubulin additionally impede spindle morphogenesis in oocytes seen follwoing SENP7 depletion.(4)Defective spindle morphogenesis attenuates the oocytes develop into metaphase I stage,and the spindle assembly checkpoint provoked by defective spindle assembly further inhibits anaphase I to proceed and thereby blocks SENP7-depleted oocytes at meiosis I stage.(5)Embryos deficient in SENP7 severely undergo defective maternal-zygote transition and progressive degeneration,resulting in rare blastocyst production.(6)The disrupted epigenetic programme on histone H3 with hyperaceylation of and hypotri-methylation of H3K9 and H3K27,restricted Rad51 C loading onto DNA lesions due to enlarged HP1α euchromatic deposition and lowed DNA 5hmC challenge the permissive status fostering zygotic DNA repair and thereby potentiates DNA damage in SENP7-depleted embryos.Moreover,the spindle catastrophe in embryos is likewise induced by SENP7 depletion.The aforementioned dysfunctions synergistically lead to the compromised development and even apoptotic death in SENP7-depleted embryos.Taken together,our study significantly pinpoints maternal SENP7 as a novel determinant in epigenetic scenario and major pathways licensing oocyte meiosis and embryo development in mammals.More importantly,our study integrates SUMOylation with other post-translational modifications on chromatin in reproductive biology,which will unequivocally providing important implications for deciphering the promiscuous protein regulation network during development and thereby improves animal reproduction and human fertility.