Premature ovarian failure in mice with oocytes lacking core 1-derived O-glycans and complex N-glycans

Suzannah A. Williams, Pamela Stanley

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Premature ovarian failure (POF) affects up to 1.4% of women under the age of 40 yr and less than 30% of cases have a known cause. Here we describe a new mouse model of POF resulting from oocyte-specific ablation of core 1-derived (mucin) O-glycans and complex and hybrid N-glycans. Females carrying floxed alleles of both the C1galt1 (T-syn) and Mgat1 glycosyltransferase genes and a ZP3Cre transgene, generate oocytes lacking complex O- and N-glycans following oocyte-specific deletion at the primary follicle stage. We previously showed that few double-mutant females are fertile, and those produce only a single small litter. Here we show that ovarian function declined rapidly in double-mutant females with less than 1% ovulating at 11 wk of age after superovulation with exogenous gonadotropins. Ovary weight was significantly decreased in double-mutant females by 3 months of age, consistent with a decrease in the number of developing follicles. FSH levels in double-mutant females were elevated at 3 months of age, and testosterone and inhibin A were decreased, showing that the loss of complex N- and O-glycans from oocyte glycoproteins affected hypothalamic-pituitary-gonadal feedback loops. The absence of developing follicles, ovary dysfunction, reduced testosterone and inhibin A, and elevated FSH in double-mutant females lacking C1galt1 and Mgat1 in oocytes represents a new mouse model for the study of follicular POF.

Original languageEnglish (US)
Pages (from-to)1057-1066
Number of pages10
JournalEndocrinology
Volume152
Issue number3
DOIs
StatePublished - Mar 2011

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Primary Ovarian Insufficiency
Oocytes
Polysaccharides
Testosterone
Ovary
Superovulation
Mucin-1
Glycosyltransferases
Gonadotropins
Transgenes
Glycoproteins
Alleles
Weights and Measures
Genes

ASJC Scopus subject areas

  • Endocrinology

Cite this

Premature ovarian failure in mice with oocytes lacking core 1-derived O-glycans and complex N-glycans. / Williams, Suzannah A.; Stanley, Pamela.

In: Endocrinology, Vol. 152, No. 3, 03.2011, p. 1057-1066.

Research output: Contribution to journalArticle

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