Premature ovarian failure in mice with oocytes lacking core 1-derived O-glycans and complex N-glycans.
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 f...
| Main Authors: | , |
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| Format: | Journal article |
| Language: | English |
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2011
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| _version_ | 1826299631704735744 |
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| author | Williams, S Stanley, P |
| author_facet | Williams, S Stanley, P |
| author_sort | Williams, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:04:53Z |
| format | Journal article |
| id | oxford-uuid:d995053f-edc1-42ae-bcd9-91b0fb947ead |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:04:53Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:d995053f-edc1-42ae-bcd9-91b0fb947ead2022-03-27T08:56:52ZPremature ovarian failure in mice with oocytes lacking core 1-derived O-glycans and complex N-glycans.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d995053f-edc1-42ae-bcd9-91b0fb947eadEnglishSymplectic Elements at Oxford2011Williams, SStanley, PPremature 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. |
| spellingShingle | Williams, S Stanley, P Premature ovarian failure in mice with oocytes lacking core 1-derived O-glycans and complex N-glycans. |
| title | Premature ovarian failure in mice with oocytes lacking core 1-derived O-glycans and complex N-glycans. |
| title_full | Premature ovarian failure in mice with oocytes lacking core 1-derived O-glycans and complex N-glycans. |
| title_fullStr | Premature ovarian failure in mice with oocytes lacking core 1-derived O-glycans and complex N-glycans. |
| title_full_unstemmed | Premature ovarian failure in mice with oocytes lacking core 1-derived O-glycans and complex N-glycans. |
| title_short | Premature ovarian failure in mice with oocytes lacking core 1-derived O-glycans and complex N-glycans. |
| title_sort | premature ovarian failure in mice with oocytes lacking core 1 derived o glycans and complex n glycans |
| work_keys_str_mv | AT williamss prematureovarianfailureinmicewithoocyteslackingcore1derivedoglycansandcomplexnglycans AT stanleyp prematureovarianfailureinmicewithoocyteslackingcore1derivedoglycansandcomplexnglycans |