Frontiers in Genetics (Jun 2021)
Identification of Novel Biallelic TLE6 Variants in Female Infertility With Preimplantation Embryonic Lethality
- Manyu Zhang,
- Manyu Zhang,
- Manyu Zhang,
- Chunyu Liu,
- Chunyu Liu,
- Chunyu Liu,
- Beili Chen,
- Beili Chen,
- Beili Chen,
- Mingrong Lv,
- Mingrong Lv,
- Mingrong Lv,
- Huijuan Zou,
- Huijuan Zou,
- Huijuan Zou,
- Yajing Liu,
- Yajing Liu,
- Yajing Liu,
- Yang Gao,
- Yang Gao,
- Yang Gao,
- Tianjuan Wang,
- Tianjuan Wang,
- Tianjuan Wang,
- Qiong Xing,
- Qiong Xing,
- Qiong Xing,
- Yutong Zhu,
- Yutong Zhu,
- Yutong Zhu,
- Huan Wu,
- Huan Wu,
- Huan Wu,
- Zhiguo Zhang,
- Zhiguo Zhang,
- Zhiguo Zhang,
- Ping Zhou,
- Ping Zhou,
- Ping Zhou,
- Zhaolian Wei,
- Zhaolian Wei,
- Zhaolian Wei,
- Xiaojin He,
- Xiaojin He,
- Xiaojin He,
- Yuping Xu,
- Yuping Xu,
- Yuping Xu,
- Yunxia Cao,
- Yunxia Cao,
- Yunxia Cao
Affiliations
- Manyu Zhang
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Manyu Zhang
- NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract Anhui Medical University, Hefei, China
- Manyu Zhang
- Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People’s Republic of China, Hefei, China
- Chunyu Liu
- Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai, China
- Chunyu Liu
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China
- Chunyu Liu
- State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
- Beili Chen
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Beili Chen
- NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract Anhui Medical University, Hefei, China
- Beili Chen
- Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People’s Republic of China, Hefei, China
- Mingrong Lv
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Mingrong Lv
- Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, China
- Mingrong Lv
- Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, China
- Huijuan Zou
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Huijuan Zou
- Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, China
- Huijuan Zou
- Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, China
- Yajing Liu
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Yajing Liu
- Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, China
- Yajing Liu
- Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, China
- Yang Gao
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Yang Gao
- Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, China
- Yang Gao
- Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, China
- Tianjuan Wang
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Tianjuan Wang
- Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, China
- Tianjuan Wang
- Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, China
- Qiong Xing
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Qiong Xing
- Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, China
- Qiong Xing
- Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, China
- Yutong Zhu
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Yutong Zhu
- Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, China
- Yutong Zhu
- Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, China
- Huan Wu
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Huan Wu
- Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, China
- Huan Wu
- Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, China
- Zhiguo Zhang
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Zhiguo Zhang
- Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, China
- Zhiguo Zhang
- Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, China
- Ping Zhou
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Ping Zhou
- Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, China
- Ping Zhou
- Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, China
- Zhaolian Wei
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Zhaolian Wei
- Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, China
- Zhaolian Wei
- Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, China
- Xiaojin He
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Xiaojin He
- NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract Anhui Medical University, Hefei, China
- Xiaojin He
- Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People’s Republic of China, Hefei, China
- Yuping Xu
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Yuping Xu
- NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract Anhui Medical University, Hefei, China
- Yuping Xu
- Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People’s Republic of China, Hefei, China
- Yunxia Cao
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Yunxia Cao
- NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract Anhui Medical University, Hefei, China
- Yunxia Cao
- Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People’s Republic of China, Hefei, China
- DOI
- https://doi.org/10.3389/fgene.2021.666136
- Journal volume & issue
-
Vol. 12
Abstract
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.
Keywords
- preimplantation embryonic lethality
- transducin-like enhancer of split 6 (TLE6)
- variant
- whole-exome sequencing
- oocyte donation
