Bi‐allelic pathogenic variants in PABPC1L cause oocyte maturation arrest and female infertility
Abstract: Oocyte maturation arrest is one of the important causes of female infertility, but the genetic factors remain largely unknown. PABPC1L, a predominant poly (A)‐binding protein in Xenopus, mouse, and human oocytes and early embryos prior to zygotic genome activation, plays a key role in translational activation of maternal mRNAs. Here, we identified compound heterozygous and homozygous variants in PABPC1L that are responsible for female infertility mainly characterized by oocyte maturation arrest in five individuals. In vitro studies demonstrated that these variants resulted in truncated proteins, reduced protein abundance, altered cytoplasmic localization, and reduced mRNA translational activation by affecting the binding of PABPC1L to mRNA. In vivo, three strains of Pabpc1l knock‐in (KI) female mice were infertile. RNA‐sequencing analysis showed abnormal activation of the Mos‐MAPK pathway in the zygotes of KI mice. Finally, we activated this pathway in mouse zygotes by injecting human MOS mRNA, and this mimicked the phenotype of KI mice. Our findings reveal the important roles of PABPC1L in human oocyte maturation and add a genetic potential candidate gene to be screened for causes of infertility.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Bi‐allelic pathogenic variants in PABPC1L cause oocyte maturation arrest and female infertility ; day:13 ; month:04 ; year:2023 ; extent:16
EMBO molecular medicine / European Molecular Biology Organization ; (13.04.2023) (gesamt 16)
- Creator
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Wang, Weijie
Guo, Jing
Shi, Juanzi
Li, Qun
Chen, Biaobang
Pan, Zhiqi
Qu, Ronggui
Fu, Jing
Shi, Rong
Xue, Xia
Mu, Jian
Zhang, Zhihua
Wu, Tianyu
Wang, Wenjing
Zhao, Lin
Li, Qiaoli
He, Lin
Sun, Xiaoxi
Sang, Qing
Lin, Ge
Wang, Lei
- DOI
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10.15252/emmm.202217177
- URN
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urn:nbn:de:101:1-2023041315324387695103
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 11:01 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Wang, Weijie
- Guo, Jing
- Shi, Juanzi
- Li, Qun
- Chen, Biaobang
- Pan, Zhiqi
- Qu, Ronggui
- Fu, Jing
- Shi, Rong
- Xue, Xia
- Mu, Jian
- Zhang, Zhihua
- Wu, Tianyu
- Wang, Wenjing
- Zhao, Lin
- Li, Qiaoli
- He, Lin
- Sun, Xiaoxi
- Sang, Qing
- Lin, Ge
- Wang, Lei
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