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Variation Screening of Zygote Arrest 1(ZAR1) in Women with Recurrent Zygote Arrest During IVF/ICSI Programs

  • Reproductive Endocrinology: Original Article
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Abstract

Human zygote arrest during in vitro culture is rare and the etiology is unclear. The oocyte-specific gene Zar1 plays an essential role in oocyte-embryo transition, and most embryos from Zar1 knockout female mice arrest at the one-cell stage. This study investigates whether maternal ZAR1 gene variations play a role in human zygote arrest. Sequence analysis of ZAR1 was conducted for 47 women with recurrent uncleaved zygotes in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles (≥ 70% zygotes uncleaved in at least 2 cycles), 93 women from IVF/ICSI cycles with normal uncleaved rate and live birth (control subset I) and 188 women with spontaneous pregnancy and live birth (control subset II). One novel synonymous variation (c.516C>T) and one novel intron variation (c.964-55A>T) of ZAR1 were identified in the zygote arrest group but not in any of the 188 controls. However, the bioinformatics analysis revealed that neither of the mutations in ZAR1 has effect on ZAR1 protein function. Compared with control subset I, the allele frequencies of rare SNPs rs117545505 and rs17609740 were significantly different in patients with zygote arrest (P = 0.047, OR = 3.66). Allele frequencies of these two SNPs were also significantly different between the case group and control subset II (P = 0.024, OR = 3.28). In conclusion, two SNPs in ZAR1 are associated with human zygote arrest, although additional proof is needed for validation.

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Data Availability

All data generated in this study are included in this manuscript.

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Acknowledgments

The authors thank all the women subjects who participated in this study.

Funding

This research was supported by the National Key Research and Development Program of China (2017YFC1001000, 2016YFC1000600); the National Natural Science Foundation of China (81430029, 81701410, 81622021, 31871509, 31571548, 31601199); the National Natural Science Foundation of Shandong Province (JQ201816); and the National Institutes of Health (R01HD085527).

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Author notes

  1. Ye Tian and Jie Yang contributed equally to this work.

Authors and Affiliations

  1. Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China

    Ye Tian, Jie Yang, Yingqian Peng, Tailai Chen, Tao Huang, Changming Zhang & Han Zhao

  2. National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, 250012, Shandong, China

    Ye Tian, Jie Yang, Yingqian Peng, Tailai Chen, Tao Huang, Changming Zhang & Han Zhao

  3. Key Laboratory for Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, 250012, Shandong, China

    Ye Tian, Jie Yang, Yingqian Peng, Tailai Chen, Tao Huang, Changming Zhang & Han Zhao

  4. Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China

    Ye Tian

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  1. Ye Tian
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Contributions

YT and HZ partially designed, executed, and drafted the manuscript; YT, JY, and TC collected all clinical data; YP, TH, LC, and CZ collected blood samples; YT, JY, and YP performed experiments; and HZ revised the article. All authors gave their final approval of the version to be published.

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Correspondence to Han Zhao.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Tian, Y., Yang, J., Peng, Y. et al. Variation Screening of Zygote Arrest 1(ZAR1) in Women with Recurrent Zygote Arrest During IVF/ICSI Programs. Reprod. Sci. 27, 2265–2270 (2020). https://doi.org/10.1007/s43032-020-00246-y

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  • DOI: https://doi.org/10.1007/s43032-020-00246-y

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