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

Shaolin Shi, Suzannah A. Williams, Antti Seppo, Henry Kurniawan, Wei Chen, Zhengyi Ye, Jamey D. Marth, Pamela Stanley

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)9920-9929
Number of pages10
JournalMolecular and Cellular Biology
Volume24
Issue number22
DOIs
StatePublished - Nov 2004

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Oogenesis
Gene Silencing
Oocytes
Polysaccharides
Embryonic Structures
Eggs
Zona Pellucida
Blastocyst
Fertilization
Recombinases
Zygote
Heterozygote
Lymphocyte Activation
Gonadotropins
Transgenes
Genes
Fertility
Glycoproteins
Mothers
Parturition

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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Inactivation of the Mgat1 gene in oocytes impairs oogenesis, but embryos lacking complex and hybrid N-glycans develop and implant. / Shi, Shaolin; Williams, Suzannah A.; Seppo, Antti; Kurniawan, Henry; Chen, Wei; Ye, Zhengyi; Marth, Jamey D.; Stanley, Pamela.

In: Molecular and Cellular Biology, Vol. 24, No. 22, 11.2004, p. 9920-9929.

Research output: Contribution to journalArticle

Shi, Shaolin ; Williams, Suzannah A. ; Seppo, Antti ; Kurniawan, Henry ; Chen, Wei ; Ye, Zhengyi ; Marth, Jamey D. ; Stanley, Pamela. / Inactivation of the Mgat1 gene in oocytes impairs oogenesis, but embryos lacking complex and hybrid N-glycans develop and implant. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 22. pp. 9920-9929.
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