NSUN2 is critical for mouse oocyte meiosis and early embryonic development

in Reproduction
Authors:
Tengteng Xu Department of Gynecology, Clinical Transformation and Application Key Lab for Obstetrics and Gynecology, Pediatrics, and Reproductive Medicine of Jiangmen, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, China
MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China
Clinical Experimental Center, Jiangmen Engineering Technology Research Center of Clinical Biobank and Translational Research, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, China

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Min Gao Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Hainan Provincial Clinical Research Center for Thalassemia, Reproductive Medical Center, International Technology Cooperation Base “China-Myanmar Joint Research Center for Prevention and Treatment of Regional Major Disease” By the Ministry of Science and Technology of China, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Key Laboratory of Reproductive Health Diseases Research and Translation of Ministry of Education, The First Affiliated Hospital, Hainan Medical University, Haikou, China

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Ling Zhang GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Medical University, Guangzhou, Guangdong, China

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Tianqi Cao MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China

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Yanling Qiu MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China

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Simiao Liu MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China

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Wenlian Wu MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China

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Yitong Zhou MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China

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Haiying Liu MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China

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Rui Zhang MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China

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Xiaohong Ruan Department of Gynecology, Clinical Transformation and Application Key Lab for Obstetrics and Gynecology, Pediatrics, and Reproductive Medicine of Jiangmen, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, China
Clinical Experimental Center, Jiangmen Engineering Technology Research Center of Clinical Biobank and Translational Research, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, China

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Junjiu Huang Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China
Key Laboratory of Reproductive Medicine of Guangdong Province, the First Affiliated Hospital and School of Life Sciences, Sun Yat-sen University, Guangzhou, China

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https://orcid.org/0000-0002-3417-1196

Correspondence should be addressed to J Huang or X Ruan: hjunjiu@mail.sysu.edu.cn or ruanxiaohong@jmszxyy.com.cn

(*T Xu, M Gao and L Zhang contributed equally to this work)

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In brief

The mechanism by which the NSUN2 mutation causes female infertility is still unclear. This study reveals the role and potential mechanism of NSUN2 in mouse oocyte maturation and early embryonic development, and provides a resource for elucidating female infertility with NSUN2 mutations.

Abstract

Biallelic variants in the NSUN2 gene cause a rare intellectual disability and female infertility in humans. However, the function and mechanism of NSUN2 during mouse oocyte meiotic maturation and early embryonic development are unknown. Here, we show that NSUN2 is important for mouse oocyte meiotic maturation and early embryonic development. Specifically, NSUN2 is required for ovarian development and oocyte meiosis, and deletion of Nsun2 reduces oocyte maturation and increases the rates of misaligned chromosomes and aberrant spindles. In addition, Nsun2 deficiency results in a low blastocyst rate and impaired blastocyst quality. Strikingly, loss of Nsun2 leads to approximately 35% of embryos being blocked at the 2-cell stage, and Nsun2 knockdown impairs zygotic genome activation at the 2-cell stage. Taken together, these findings suggest that NSUN2 plays a critical role in mouse oocyte meiotic maturation and early embryonic development, and provide key resources for elucidating female infertility with NSUN2 mutations.

 

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