title: Essential role of maternal UCHL1 and UCHL3 in fertilization and preimplantation embryo development.
abstract: Post-translational protein modification by ubiquitination, a signal for lysosomal or proteasomal proteolysis, can be regulated and reversed by deubiquitinating enzymes (DUBs). This study examined the roles of UCHL1 and UCHL3, two members of ubiquitin C-terminal hydrolase (UCH) family of DUBs, in murine fertilization and preimplantation development. Before fertilization, these proteins were associated with the oocyte cortex (UCHL1) and meiotic spindle (UCHL3). Intracytoplasmic injection of the general UCH-family inhibitor ubiquitin-aldehyde (UBAL) or antibodies against UCHL3 into mature metaphase II oocytes blocked fertilization by reducing sperm penetration of the zona pellucida and incorporation into the ooplasm, suggesting a role for cortical UCHL1 in sperm incorporation. Both UBAL and antibodies against UCHL1 injected at the onset of oocyte maturation (germinal vesicle stage) reduced the fertilizing ability of oocytes. The subfertile Uchl1(gad-/-) mutant mice showed an intriguing pattern of switched UCH localization, with UCHL3 replacing UCHL1 in the oocyte cortex. While fertilization defects were not observed, the embryos from homozygous Uchl1(gad-/-) mutant females failed to undergo morula compaction and did not form blastocysts in vivo, indicating a maternal effect related to UCHL1 deficiency. We conclude that the activity of oocyte UCHs contributes to fertilization and embryogenesis by regulating the physiology of the oocyte and blastomere cortex.
authors.affiliation: The Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, Pennsylvania, USA.
authors.forename: Namdori R
authors.initials: NR
authors.lastname: Mtango
authors.forename: Miriam
authors.initials: M
authors.lastname: Sutovsky
authors.forename: Andrej
authors.initials: A
authors.lastname: Susor
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Zhong
authors.forename: Keith E
authors.initials: KE
authors.lastname: Latham
authors.forename: Peter
authors.initials: P
authors.lastname: Sutovsky
mesh_terms: D000818:Animals; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D005260:Female; D005306:Fertilization / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009865:Oocytes / Q000187:drug effects / Q000201:enzymology; D009866:Oogenesis / Q000502:physiology; D011247:Pregnancy; D043222:Ubiquitin Thiolesterase / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014452:Ubiquitins / Q000494:pharmacology
chemical_list: C526917:UCHL3 protein, mouse; D014452:Ubiquitins; C051927:ubiquitin-aldehyde; D043222:Ubiquitin Thiolesterase; C496976:Uchl1 protein, mouse