NLRP7 participates in the human subcortical maternal complex and its variants cause female infertility characterized by early embryo arrest
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature..
Successful human reproduction requires normal oocyte maturation, fertilization, and early embryo development. Early embryo arrest is a common phenomenon leading to female infertility, but the genetic basis is largely unknown. NLR family pyrin domain-containing 7 (NLRP7) is a member of the NLRP subfamily. Previous studies have shown that variants of NLRP7 are one of the crucial causes of female recurrent hydatidiform mole, but whether NLRP7 variants can directly affect early embryo development is unclear. We performed whole-exome sequencing in patients who experienced early embryo arrest, and five heterozygous variants (c.251G > A, c.1258G > A, c.1441G > A, c. 2227G > A, c.2323C > T) of NLRP7 were identified in affected individuals. Plasmids of NLRP7 and subcortical maternal complex components were overexpressed in 293 T cells, and Co-IP experiments showed that NLRP7 interacted with NLRP5, TLE6, PADI6, NLRP2, KHDC3L, OOEP, and ZBED3. Injecting complementary RNAs in mouse oocytes and early embryos showed that NLRP7 variants influenced the oocyte quality and some of the variants significantly affected early embryo development. These findings contribute to our understanding of the role of NLRP7 in human early embryo development and provide a new genetic marker for clinical early embryo arrest patients. KEY MESSAGES: Five heterozygous variants of NLRP7 (c.1441G > A; 2227G > A; c.251G > A; c.1258G > A; c.2323C > T) were identified in five infertile patients who experienced early embryo arrest. NLRP7 is a component of human subcortical maternal complex. NLRP7 variants lead to poor quality of oocytes and early embryo development arrest. This study provides a new genetic marker for clinical early embryo arrest patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:101 |
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| Enthalten in: |
Journal of molecular medicine (Berlin, Germany) - 101(2023), 6 vom: 16. Juni, Seite 717-729 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Han, Jian [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.06.2023 Date Revised 03.07.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00109-023-02322-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM356514773 |
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| 245 | 1 | 0 | |a NLRP7 participates in the human subcortical maternal complex and its variants cause female infertility characterized by early embryo arrest |
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| 520 | |a © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. | ||
| 520 | |a Successful human reproduction requires normal oocyte maturation, fertilization, and early embryo development. Early embryo arrest is a common phenomenon leading to female infertility, but the genetic basis is largely unknown. NLR family pyrin domain-containing 7 (NLRP7) is a member of the NLRP subfamily. Previous studies have shown that variants of NLRP7 are one of the crucial causes of female recurrent hydatidiform mole, but whether NLRP7 variants can directly affect early embryo development is unclear. We performed whole-exome sequencing in patients who experienced early embryo arrest, and five heterozygous variants (c.251G > A, c.1258G > A, c.1441G > A, c. 2227G > A, c.2323C > T) of NLRP7 were identified in affected individuals. Plasmids of NLRP7 and subcortical maternal complex components were overexpressed in 293 T cells, and Co-IP experiments showed that NLRP7 interacted with NLRP5, TLE6, PADI6, NLRP2, KHDC3L, OOEP, and ZBED3. Injecting complementary RNAs in mouse oocytes and early embryos showed that NLRP7 variants influenced the oocyte quality and some of the variants significantly affected early embryo development. These findings contribute to our understanding of the role of NLRP7 in human early embryo development and provide a new genetic marker for clinical early embryo arrest patients. KEY MESSAGES: Five heterozygous variants of NLRP7 (c.1441G > A; 2227G > A; c.251G > A; c.1258G > A; c.2323C > T) were identified in five infertile patients who experienced early embryo arrest. NLRP7 is a component of human subcortical maternal complex. NLRP7 variants lead to poor quality of oocytes and early embryo development arrest. This study provides a new genetic marker for clinical early embryo arrest patients | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Early embryo arrest | |
| 650 | 4 | |a Human infertility | |
| 650 | 4 | |a NLRP7 | |
| 650 | 4 | |a Oocyte quality | |
| 650 | 4 | |a SCMC | |
| 650 | 4 | |a Whole-exome sequencing | |
| 650 | 7 | |a Genetic Markers |2 NLM | |
| 650 | 7 | |a NLRP7 protein, human |2 NLM | |
| 650 | 7 | |a Adaptor Proteins, Signal Transducing |2 NLM | |
| 650 | 7 | |a Nlrp2 protein, mouse |2 NLM | |
| 650 | 7 | |a Apoptosis Regulatory Proteins |2 NLM | |
| 700 | 1 | |a Zhang, Nana |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Qiqi |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Xiaodan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Congjing |e verfasserin |4 aut | |
| 700 | 1 | |a Rui, Ximan |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Chun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Junqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Ling, Xiufeng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Guan, Yichun |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Qingxia |e verfasserin |4 aut | |
| 700 | 1 | |a Huo, Ran |e verfasserin |4 aut | |
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