Maternal SENP7 programs meiosis architecture and embryo survival in mouse.
Understanding the mechanisms underlying abnormal egg production and pregnancy loss is significant for human fertility. SENP7, a SUMO poly-chain editing enzyme, has been regarded as a mitotic regulator of heterochromatin integrity and DNA repair. Herein, we report the roles of SENP7 in mammalian reproductive scenario. Mouse oocytes deficient in SENP7 experienced meiotic arrest at prophase I and metaphase I stages, causing a substantial decrease of mature eggs. Hyperaceylation and hypomethylation of histone H3 and up-regulation of Cdc14B/C accompanied by down-regulation of CyclinB1 and CyclinB2 were further recognized as contributors to defective M-phase entry and spindle assembly in oocytes. The spindle assembly checkpoint activated by defective spindle morphogenesis, which was also caused by mislocalization and ubiquitylation-mediated proteasomal degradation of γ-tubulin, blocked oocytes at meiosis I stage. SENP7-depleted embryos exhibited severely defective maternal-zygotic transition and progressive degeneration, resulting in nearly no blastocyst production. The disrupted epigenetic landscape on histone H3 restricted Rad51C loading onto DNA lesions due to elevated HP1α euchromatic deposition, and reduced DNA 5hmC challenged the permissive status for zygotic DNA repair, which induce embryo death. Our study pinpoints SENP7 as a novel determinant in epigenetic programming and major pathways that govern oocyte and embryo development programs in mammals.
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China.
Chun-Jie
CJ
Huang
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China.
Di
D
Wu
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China.
Xiao-Fei
XF
Jiao
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China.
Faheem Ahmed
FA
Khan
Reproductive Medicine Center of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, PR China.
Cheng-Liang
CL
Xiong
Second Affiliated Hospital and Center of Reproductive Medicine, Wenzhou Medical University, Wenzhou 330302, PR China.
Xiao-Ming
XM
Liu
Reproductive Medicine Center, Wuhan University Renmin Hospital, Wuhan 430060, PR China.
Jing
J
Yang
Reproductive Medicine Center, Wuhan University Renmin Hospital, Wuhan 430060, PR China.
Tai-Lang
TL
Yin
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China. Electronic address: lijunhuo@yahoo.com.
Li-Jun
LJ
Huo
D000818:Animals; D001755:Blastocyst / Q000378:metabolism*; D002478:Cells, Cultured; D000090266:Chromobox Protein Homolog 5; D056744:Cyclin B1 / Q000378:metabolism; D056765:Cyclin B2 / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D006657:Histones / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints; D000072741:Maternal Inheritance; D008540:Meiosis; D051379:Mice; D009865:Oocytes / Q000378:metabolism; D011247:Pregnancy; D014404:Tubulin / Q000378:metabolism; D015053:Zygote / Q000378:metabolism
C000715594:CBX5 protein, human; D056744:Cyclin B1; D056765:Cyclin B2; D006657:Histones; D014404:Tubulin; D000090266:Chromobox Protein Homolog 5; D010450:Endopeptidases; C572283:SENP7 protein, mouse
DNA damage; Epigenetic program; M-phase entry; Preimplantation development; SUMOylation; Spindle morphogenesis