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Identification of Novel Biallelic TLE6 Variants in Female Infertility With Preimplantation Embryonic Lethality

Preimplantation embryonic lethality is a rare cause of primary female infertility. It has been reported that variants in the transducin-like enhancer of split 6 (TLE6) gene can lead to preimplantation embryonic lethality. However, the incidence of TLE6 variants in patients with preimplantation embry...

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Autores principales: Zhang, Manyu, Liu, Chunyu, Chen, Beili, Lv, Mingrong, Zou, Huijuan, Liu, Yajing, Gao, Yang, Wang, Tianjuan, Xing, Qiong, Zhu, Yutong, Wu, Huan, Zhang, Zhiguo, Zhou, Ping, Wei, Zhaolian, He, Xiaojin, Xu, Yuping, Cao, Yunxia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226231/
https://www.ncbi.nlm.nih.gov/pubmed/34178031
http://dx.doi.org/10.3389/fgene.2021.666136
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author Zhang, Manyu
Liu, Chunyu
Chen, Beili
Lv, Mingrong
Zou, Huijuan
Liu, Yajing
Gao, Yang
Wang, Tianjuan
Xing, Qiong
Zhu, Yutong
Wu, Huan
Zhang, Zhiguo
Zhou, Ping
Wei, Zhaolian
He, Xiaojin
Xu, Yuping
Cao, Yunxia
author_facet Zhang, Manyu
Liu, Chunyu
Chen, Beili
Lv, Mingrong
Zou, Huijuan
Liu, Yajing
Gao, Yang
Wang, Tianjuan
Xing, Qiong
Zhu, Yutong
Wu, Huan
Zhang, Zhiguo
Zhou, Ping
Wei, Zhaolian
He, Xiaojin
Xu, Yuping
Cao, Yunxia
author_sort Zhang, Manyu
collection PubMed
description Preimplantation embryonic lethality is a rare cause of primary female infertility. It has been reported that variants in the transducin-like enhancer of split 6 (TLE6) gene can lead to preimplantation embryonic lethality. However, the incidence of TLE6 variants in patients with preimplantation embryonic lethality is not fully understood. In this study, we identified four patients carrying novel biallelic TLE6 variants in a cohort of 28 patients with preimplantation embryonic lethality by whole-exome sequencing and bioinformatics analysis, accounting for 14.29% (4/28) of the cohort. Immunofluorescence showed that the TLE6 levels in oocytes from patients were much lower than in normal control oocytes, suggesting that the variants result in the lower expression of the TLE6 protein in oocytes. In addition, a retrospective analysis showed that the four patients underwent a total of nine failures of in vitro fertilization and intracytoplasmic sperm injection attempts, and one of them became pregnant on the first attempt using donated oocytes. Our study extends the genetic spectrum of female infertility caused by variants in TLE6 and further confirms previously reported findings that TLE6 plays an essential role in early embryonic development. In such case, oocyte donation may be the preferred treatment.
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spelling pubmed-82262312021-06-26 Identification of Novel Biallelic TLE6 Variants in Female Infertility With Preimplantation Embryonic Lethality Zhang, Manyu Liu, Chunyu Chen, Beili Lv, Mingrong Zou, Huijuan Liu, Yajing Gao, Yang Wang, Tianjuan Xing, Qiong Zhu, Yutong Wu, Huan Zhang, Zhiguo Zhou, Ping Wei, Zhaolian He, Xiaojin Xu, Yuping Cao, Yunxia Front Genet Genetics Preimplantation embryonic lethality is a rare cause of primary female infertility. It has been reported that variants in the transducin-like enhancer of split 6 (TLE6) gene can lead to preimplantation embryonic lethality. However, the incidence of TLE6 variants in patients with preimplantation embryonic lethality is not fully understood. In this study, we identified four patients carrying novel biallelic TLE6 variants in a cohort of 28 patients with preimplantation embryonic lethality by whole-exome sequencing and bioinformatics analysis, accounting for 14.29% (4/28) of the cohort. Immunofluorescence showed that the TLE6 levels in oocytes from patients were much lower than in normal control oocytes, suggesting that the variants result in the lower expression of the TLE6 protein in oocytes. In addition, a retrospective analysis showed that the four patients underwent a total of nine failures of in vitro fertilization and intracytoplasmic sperm injection attempts, and one of them became pregnant on the first attempt using donated oocytes. Our study extends the genetic spectrum of female infertility caused by variants in TLE6 and further confirms previously reported findings that TLE6 plays an essential role in early embryonic development. In such case, oocyte donation may be the preferred treatment. Frontiers Media S.A. 2021-06-11 /pmc/articles/PMC8226231/ /pubmed/34178031 http://dx.doi.org/10.3389/fgene.2021.666136 Text en Copyright © 2021 Zhang, Liu, Chen, Lv, Zou, Liu, Gao, Wang, Xing, Zhu, Wu, Zhang, Zhou, Wei, He, Xu and Cao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Zhang, Manyu
Liu, Chunyu
Chen, Beili
Lv, Mingrong
Zou, Huijuan
Liu, Yajing
Gao, Yang
Wang, Tianjuan
Xing, Qiong
Zhu, Yutong
Wu, Huan
Zhang, Zhiguo
Zhou, Ping
Wei, Zhaolian
He, Xiaojin
Xu, Yuping
Cao, Yunxia
Identification of Novel Biallelic TLE6 Variants in Female Infertility With Preimplantation Embryonic Lethality
title Identification of Novel Biallelic TLE6 Variants in Female Infertility With Preimplantation Embryonic Lethality
title_full Identification of Novel Biallelic TLE6 Variants in Female Infertility With Preimplantation Embryonic Lethality
title_fullStr Identification of Novel Biallelic TLE6 Variants in Female Infertility With Preimplantation Embryonic Lethality
title_full_unstemmed Identification of Novel Biallelic TLE6 Variants in Female Infertility With Preimplantation Embryonic Lethality
title_short Identification of Novel Biallelic TLE6 Variants in Female Infertility With Preimplantation Embryonic Lethality
title_sort identification of novel biallelic tle6 variants in female infertility with preimplantation embryonic lethality
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226231/
https://www.ncbi.nlm.nih.gov/pubmed/34178031
http://dx.doi.org/10.3389/fgene.2021.666136
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