2. Academic Validation
  3. Novel variants in MEI1 cause female infertility characterized by early embryonic arrest and implantation failure

Novel variants in MEI1 cause female infertility characterized by early embryonic arrest and implantation failure

  • J Assist Reprod Genet. 2025 Nov 29. doi: 10.1007/s10815-025-03748-3.
Beili Chen # 1 2 3,  Menghan Chai # 1 2,  Yutong Zhu # 4,  Qiannan Zhang 1 2,  Dandan Yang 1 2,  Min Xiong 1 2,  Yunxia Cao 1 2,  Zhaolian Wei 1 2,  Lin Li 5,  Zhiguo Zhang 6 7 8 9,  Yuping Xu 10 11
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230032, China.
  • 2 NHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, China.
  • 3 Innovation Research Institute of Engineering Medicine and Medical Equipment, Hefei, 230032, China.
  • 4 Reproductive Medicine Center, Anhui No. 2 Provincial People's Hospital, Hefei, 230041, Anhui, China.
  • 5 Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100006, China. [email protected].
  • 6 Department of Obstetrics and Gynecology, Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230032, China. [email protected].
  • 7 NHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, China. [email protected].
  • 8 Innovation Research Institute of Engineering Medicine and Medical Equipment, Hefei, 230032, China. [email protected].
  • 9 Department of Biomedical Engineering, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, China. [email protected].
  • 10 Department of Obstetrics and Gynecology, Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230032, China. [email protected].
  • 11 NHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, China. [email protected].
  • # Contributed equally.
PMID: 41315153 DOI: 10.1007/s10815-025-03748-3
Abstract

Purpose: Early embryonic arrest (EEA) and implantation failure are prevalent causes of female infertility, with genetic factors playing a significant role. MEI1 is a crucial gene for meiotic chromosome synapsis and is essential for the formation of double-strand breaks (DSBs) during germ cell meiosis. MEI1 variants contribute to EEA and implantation failure. In this study, we reported newly identified mutations in MEI1 that broaden the genetic spectrum associated with embryonic abnormalities.

Methods: Female patients with primary infertility characterized by EEA and implantation failure were recruited, and peripheral blood samples were collected. Whole-exome Sequencing was performed, and the identified variants were confirmed by Sanger Sequencing. Bioinformatics tools were used to predict the pathogenicity of these variants. Wild-type and mutant plasmids were constructed in vitro and transfected into HEK293T cells. The effects of the variants on the expression and function of MEI1 were investigated via real-time quantitative PCR, western blotting, and immunofluorescence assays.

Results: We identified a novel homozygous variant and a compound heterozygous variant in MEI1 from two unrelated families. Analysis using multiple bioinformatics tools revealed that these variants are rare and may be deleterious. In vitro experiments revealed that these mutations do not alter the subcellular localization of MEI1 but significantly affect its mRNA and protein expression levels, potentially leading to impaired protein function.

Conclusion: These biallelic variants in MEI1 were associated with EEA and implantation failure. Our findings expand the known mutation spectrum of MEI1 and provide further evidence supporting the causal relationship between MEI1 variants and female infertility.

Keywords

Early embryonic arrest; Female infertility; Gene mutation; Implantation failure; MEI1.

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