Inactivation of the Mgat1 gene in oocytes impairs oogenesis, but embryos lacking complex and hybrid N-glycans develop and implant

S Shi, SA Williams, A Seppo, H Kurniawan… - … and cellular biology, 2004 - Am Soc Microbiol
S Shi, SA Williams, A Seppo, H Kurniawan, W Chen, Z Ye, JD Marth, P Stanley
Molecular and cellular biology, 2004Am Soc Microbiol
Complex and hybrid N-glycans contain sugar residues that have been implicated in
fertilization, compaction of the embryo, and implantation. Inactivation of the Mgat1 gene
responsible for their synthesis is embryonic lethal, but homozygous mutant blastocysts are
phenotypically normal due to the presence of maternal Mgat1 gene transcripts. To identify
roles for complex and hybrid N-glycans in oogenesis and preimplantation development, the
Mgat1 gene in oocytes was deleted by using a ZP3Cre recombinase transgene. All mutant …
Abstract
Complex and hybrid N-glycans contain sugar residues that have been implicated in fertilization, compaction of the embryo, and implantation. Inactivation of the Mgat1 gene responsible for their synthesis is embryonic lethal, but homozygous mutant blastocysts are phenotypically normal due to the presence of maternal Mgat1 gene transcripts. To identify roles for complex and hybrid N-glycans in oogenesis and preimplantation development, the Mgat1 gene in oocytes was deleted by using a ZP3Cre recombinase transgene. All mutant oocytes had an altered zona pellucida (ZP) that was thinner than the control ZP, and they did not possess complex N-glycans but contained ZP1, ZP2, and ZP3 glycoproteins. Mutant eggs were fertilized, all embryos implanted, and heterozygotes developed to birth. However, mutant females had decreased fertility, yielded fewer eggs after stimulation with gonadotropins, and produced a reduced number of preimplantation embryos and less progeny than controls. About 25% of embryonic day 3.5 (E3. 5) embryos derived from mutant eggs were severely retarded in development, even when they were heterozygous and expressed complex N-glycans. Thus, a proportion of Mgat1−/− oocytes were developmentally compromised. Surprisingly, mutant eggs also gave rise to Mgat1−/− embryos that developed normally, implanted, and progressed to E9. 5. Therefore, complex or hybrid N-glycans are required at some stage of oogenesis for the generation of a developmentally competent oocyte, but fertilization, blastogenesis, and implantation may proceed in their absence.
American Society for Microbiology