DPAGT1‐Mediated Protein N‐Glycosylation Is Indispensable for Oocyte and Follicle Development in Mice
Abstract Post‐translational modification of proteins by N‐linked glycosylation is crucial for many life processes. However, the exact contribution of N‐glycosylation to mammalian female reproduction remains largely undefined. Here, DPAGT1, the enzyme that catalyzes the first step of protein N‐glycos...
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| Format: | Article |
| Language: | English |
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Wiley
2020-07-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202000531 |
| _version_ | 1811299333190975488 |
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| author | Hui Li Liji You Yufeng Tian Jing Guo Xianbao Fang Chenmin Zhou Lanying Shi You‐Qiang Su |
| author_facet | Hui Li Liji You Yufeng Tian Jing Guo Xianbao Fang Chenmin Zhou Lanying Shi You‐Qiang Su |
| author_sort | Hui Li |
| collection | DOAJ |
| description | Abstract Post‐translational modification of proteins by N‐linked glycosylation is crucial for many life processes. However, the exact contribution of N‐glycosylation to mammalian female reproduction remains largely undefined. Here, DPAGT1, the enzyme that catalyzes the first step of protein N‐glycosylation, is identified to be indispensable for oocyte development in mice. Dpagt1 missense mutation (c. 497A>G; p. Asp166Gly) causes female subfertility without grossly affecting other functions. Mutant females ovulate fewer eggs owing to defective development of growing follicles. Mutant oocytes have a thin and fragile zona pellucida (ZP) due to the reduction in glycosylation of ZP proteins, and display poor developmental competence after fertilization in vitro. Moreover, completion of the first meiosis is accelerated in mutant oocytes, which is coincident with the elevation of aneuploidy. Mechanistically, transcriptomic analysis reveals the downregulation of a number of transcripts essential for oocyte meiotic progression and preimplantation development (e.g., Pttgt1, Esco2, Orc6, and Npm2) in mutant oocytes, which could account for the defects observed. Furthermore, conditional knockout of Dpagt1 in oocytes recapitulates the phenotypes observed in Dpagt1 mutant females, and causes complete infertility. Taken together, these data indicate that protein N‐glycosylation in oocytes is essential for female fertility in mammals by specific control of oocyte development. |
| first_indexed | 2024-04-13T06:34:38Z |
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| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-13T06:34:38Z |
| publishDate | 2020-07-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj.art-4bf1517a780d46f4a29cc4a0154e0a7f2022-12-22T02:57:58ZengWileyAdvanced Science2198-38442020-07-01714n/an/a10.1002/advs.202000531DPAGT1‐Mediated Protein N‐Glycosylation Is Indispensable for Oocyte and Follicle Development in MiceHui Li0Liji You1Yufeng Tian2Jing Guo3Xianbao Fang4Chenmin Zhou5Lanying Shi6You‐Qiang Su7State Key Laboratory of Reproductive Medicine Nanjing Medical University Nanjing 211166 P. R. ChinaState Key Laboratory of Reproductive Medicine Nanjing Medical University Nanjing 211166 P. R. ChinaState Key Laboratory of Reproductive Medicine Nanjing Medical University Nanjing 211166 P. R. ChinaState Key Laboratory of Reproductive Medicine Nanjing Medical University Nanjing 211166 P. R. ChinaState Key Laboratory of Reproductive Medicine Nanjing Medical University Nanjing 211166 P. R. ChinaState Key Laboratory of Reproductive Medicine Nanjing Medical University Nanjing 211166 P. R. ChinaState Key Laboratory of Reproductive Medicine Nanjing Medical University Nanjing 211166 P. R. ChinaState Key Laboratory of Reproductive Medicine Nanjing Medical University Nanjing 211166 P. R. ChinaAbstract Post‐translational modification of proteins by N‐linked glycosylation is crucial for many life processes. However, the exact contribution of N‐glycosylation to mammalian female reproduction remains largely undefined. Here, DPAGT1, the enzyme that catalyzes the first step of protein N‐glycosylation, is identified to be indispensable for oocyte development in mice. Dpagt1 missense mutation (c. 497A>G; p. Asp166Gly) causes female subfertility without grossly affecting other functions. Mutant females ovulate fewer eggs owing to defective development of growing follicles. Mutant oocytes have a thin and fragile zona pellucida (ZP) due to the reduction in glycosylation of ZP proteins, and display poor developmental competence after fertilization in vitro. Moreover, completion of the first meiosis is accelerated in mutant oocytes, which is coincident with the elevation of aneuploidy. Mechanistically, transcriptomic analysis reveals the downregulation of a number of transcripts essential for oocyte meiotic progression and preimplantation development (e.g., Pttgt1, Esco2, Orc6, and Npm2) in mutant oocytes, which could account for the defects observed. Furthermore, conditional knockout of Dpagt1 in oocytes recapitulates the phenotypes observed in Dpagt1 mutant females, and causes complete infertility. Taken together, these data indicate that protein N‐glycosylation in oocytes is essential for female fertility in mammals by specific control of oocyte development.https://doi.org/10.1002/advs.202000531DPAGT1female infertilitymeiosisN‐glycosylationoocyte quality |
| spellingShingle | Hui Li Liji You Yufeng Tian Jing Guo Xianbao Fang Chenmin Zhou Lanying Shi You‐Qiang Su DPAGT1‐Mediated Protein N‐Glycosylation Is Indispensable for Oocyte and Follicle Development in Mice Advanced Science DPAGT1 female infertility meiosis N‐glycosylation oocyte quality |
| title | DPAGT1‐Mediated Protein N‐Glycosylation Is Indispensable for Oocyte and Follicle Development in Mice |
| title_full | DPAGT1‐Mediated Protein N‐Glycosylation Is Indispensable for Oocyte and Follicle Development in Mice |
| title_fullStr | DPAGT1‐Mediated Protein N‐Glycosylation Is Indispensable for Oocyte and Follicle Development in Mice |
| title_full_unstemmed | DPAGT1‐Mediated Protein N‐Glycosylation Is Indispensable for Oocyte and Follicle Development in Mice |
| title_short | DPAGT1‐Mediated Protein N‐Glycosylation Is Indispensable for Oocyte and Follicle Development in Mice |
| title_sort | dpagt1 mediated protein n glycosylation is indispensable for oocyte and follicle development in mice |
| topic | DPAGT1 female infertility meiosis N‐glycosylation oocyte quality |
| url | https://doi.org/10.1002/advs.202000531 |
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