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Mutation analysis of the TUBB8 gene in primary infertile women with oocyte maturation arrest
BACKGROUND: Oocyte maturation arrest at metaphase I leads to fertilization failure in humans. In early embryos, the tubulin beta 8 class VIII (TUBB8) encodes a β-tubulin isotype and aids in the assembling of the human oocyte spindle. Mutations in the TUBB8 potentially interfere with human oocyte mat...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8969352/ https://www.ncbi.nlm.nih.gov/pubmed/35354490 http://dx.doi.org/10.1186/s13048-022-00971-9 |
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author | Yao, Zhongyuan Zeng, Jun Zhu, Huimin Zhao, Jing Wang, Xiaoxia Xia, Qiuping Li, Yanping Wu, Lingqian |
author_facet | Yao, Zhongyuan Zeng, Jun Zhu, Huimin Zhao, Jing Wang, Xiaoxia Xia, Qiuping Li, Yanping Wu, Lingqian |
author_sort | Yao, Zhongyuan |
collection | PubMed |
description | BACKGROUND: Oocyte maturation arrest at metaphase I leads to fertilization failure in humans. In early embryos, the tubulin beta 8 class VIII (TUBB8) encodes a β-tubulin isotype and aids in the assembling of the human oocyte spindle. Mutations in the TUBB8 potentially interfere with human oocyte maturation—a crucial prerequisite for fertilization and subsequent embryonic development. This study aims to investigate the novel mutations in TUBB8 and their prevalence. RESULTS: Hundred fertile women (controls) and eleven infertile women with oocyte maturation arrest were chosen for the study. A total of five TUBB8 heterozygous/homozygous mutations were found in eleven infertile females (p.A313V, p.C239W, p.R251Q, p.P358L, and p.G96R). The Exome Aggregation Consortium (ExAC), SIFT, and PolyPhen-2 analyses revealed that p. A313V has unknown pathogenicity and p.C239W, p.R251Q, p.P358L, and p.G96R have possible pathogenicity. The wild-type (WT) and four mutant gene constructs were transfected to Hela cells. The Western blot analysis indicates that the TUBB8 expression of the p.C239W, p.R251Q, and p.G96R mutations was significantly decreased than that of WT. The immunofluorescence assay showed that the Hela cells transfected with either p.C239W, p.R251Q, or p.G96R mutations exhibited the disrupted microtubule structure, revealing a significant difference in the organization of the microtubule network compared to the WT. CONCLUSIONS: We identified three novel variants and two reported variants out of 11 infertile women with oocyte metaphase I arrest. According to the present data, TUBB8 gene variants account for 31.96% of all participants (109/341) with oocyte maturation arrest. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-022-00971-9. |
format | Online Article Text |
id | pubmed-8969352 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-89693522022-04-01 Mutation analysis of the TUBB8 gene in primary infertile women with oocyte maturation arrest Yao, Zhongyuan Zeng, Jun Zhu, Huimin Zhao, Jing Wang, Xiaoxia Xia, Qiuping Li, Yanping Wu, Lingqian J Ovarian Res Research BACKGROUND: Oocyte maturation arrest at metaphase I leads to fertilization failure in humans. In early embryos, the tubulin beta 8 class VIII (TUBB8) encodes a β-tubulin isotype and aids in the assembling of the human oocyte spindle. Mutations in the TUBB8 potentially interfere with human oocyte maturation—a crucial prerequisite for fertilization and subsequent embryonic development. This study aims to investigate the novel mutations in TUBB8 and their prevalence. RESULTS: Hundred fertile women (controls) and eleven infertile women with oocyte maturation arrest were chosen for the study. A total of five TUBB8 heterozygous/homozygous mutations were found in eleven infertile females (p.A313V, p.C239W, p.R251Q, p.P358L, and p.G96R). The Exome Aggregation Consortium (ExAC), SIFT, and PolyPhen-2 analyses revealed that p. A313V has unknown pathogenicity and p.C239W, p.R251Q, p.P358L, and p.G96R have possible pathogenicity. The wild-type (WT) and four mutant gene constructs were transfected to Hela cells. The Western blot analysis indicates that the TUBB8 expression of the p.C239W, p.R251Q, and p.G96R mutations was significantly decreased than that of WT. The immunofluorescence assay showed that the Hela cells transfected with either p.C239W, p.R251Q, or p.G96R mutations exhibited the disrupted microtubule structure, revealing a significant difference in the organization of the microtubule network compared to the WT. CONCLUSIONS: We identified three novel variants and two reported variants out of 11 infertile women with oocyte metaphase I arrest. According to the present data, TUBB8 gene variants account for 31.96% of all participants (109/341) with oocyte maturation arrest. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-022-00971-9. BioMed Central 2022-03-30 /pmc/articles/PMC8969352/ /pubmed/35354490 http://dx.doi.org/10.1186/s13048-022-00971-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Yao, Zhongyuan Zeng, Jun Zhu, Huimin Zhao, Jing Wang, Xiaoxia Xia, Qiuping Li, Yanping Wu, Lingqian Mutation analysis of the TUBB8 gene in primary infertile women with oocyte maturation arrest |
title | Mutation analysis of the TUBB8 gene in primary infertile women with oocyte maturation arrest |
title_full | Mutation analysis of the TUBB8 gene in primary infertile women with oocyte maturation arrest |
title_fullStr | Mutation analysis of the TUBB8 gene in primary infertile women with oocyte maturation arrest |
title_full_unstemmed | Mutation analysis of the TUBB8 gene in primary infertile women with oocyte maturation arrest |
title_short | Mutation analysis of the TUBB8 gene in primary infertile women with oocyte maturation arrest |
title_sort | mutation analysis of the tubb8 gene in primary infertile women with oocyte maturation arrest |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8969352/ https://www.ncbi.nlm.nih.gov/pubmed/35354490 http://dx.doi.org/10.1186/s13048-022-00971-9 |
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