TUBB8 Mutations Cause Female Infertility with Large Polar Body Oocyte and Fertilization Failure

Tubulin beta 8 class VIII ( TUBB8 ) is a special β-tubulin isotype that mainly expressed in primate oocytes and early embryos and identified as the disease-causing gene of human oocyte maturation arrest. To identify the disease-causing genes in 2 patients with female infertility due to large polar b...

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Published in:Reproductive sciences (Thousand Oaks, Calif.) Calif.), 2021-10, Vol.28 (10), p.2942-2950
Main Authors: Liu, Zhenxing, Xi, Qingsong, Zhu, Lixia, Yang, Xue, Jin, Lei, Wang, Jiarui, Zhang, Tao, Zhou, Xiaopei, Zhang, Dazhi, Peng, Xuejie, Luo, Yalin, Li, Zhou, Zhang, Xianqin
Format: Article
Language:English
Subjects:
Adult
Embryology
Female
Fertilization - genetics
Genetics: Original Article
HEK293 Cells
HeLa Cells
Humans
Infertility, Female - diagnosis
Infertility, Female - genetics
Medicine
Medicine & Public Health
Mutation, Missense - genetics
Obstetrics/Perinatology/Midwifery
Oocytes - physiology
Pedigree
Polar Bodies - physiology
Protein Structure, Secondary
Reproductive Medicine
Tubulin - genetics
Whole Exome Sequencing - methods
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Summary:Tubulin beta 8 class VIII ( TUBB8 ) is a special β-tubulin isotype that mainly expressed in primate oocytes and early embryos and identified as the disease-causing gene of human oocyte maturation arrest. To identify the disease-causing genes in 2 patients with female infertility due to large polar body oocyte or fertilization failure, whole-exome sequencing was performed on the patients and available family members. We identified a novel heterozygous missense mutation c.817C>G (p.L273V) and a recently reported heterozygous missense mutation c.608A>G (p.D203G) in TUBB8 from two patients, respectively. We found oocyte with a large polar body in the patient who carried the p.D203G mutation in TUBB8 . Bioinformatics analysis showed that these two mutations are harmful. The results of western blot and RT-PCR experiments showed that the D203G mutation caused a significant decrease in the expression of TUBB8 , and immunostaining showed that the TUBB8 mutation caused abnormal microtubule morphology. These findings suggest that TUBB8 mutations resulted in oocyte with a large polar body and fertilization failure in patients.
ISSN:1933-7191
1933-7205
DOI:10.1007/s43032-021-00633-z