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.
Highlights
Infertility affects about 10–15% of couples worldwide and has become an increasingly common health problem (Tamrakar and Bastakoti, 2019)
All of the 28 infertile women recruited in our study satisfied the following enrolled criteria for preimplantation embryonic lethality (PEL): (1) women aged 20–40 years were diagnosed with primary infertility; (2) normal ovulatory status and the morphology of the oocytes without obvious abnormalities; (3) more than once failure of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles caused by embryonic arrest
In the present study, using whole-exome sequencing (WES) and bioinformatics analyses, we identified biallelic transducin-like enhancer of split 6 (TLE6) variants in 4 patients from a cohort of 28 infertile women with PEL, accounting for 14.29% of the cohort
Summary
Infertility affects about 10–15% of couples worldwide and has become an increasingly common health problem (Tamrakar and Bastakoti, 2019). Biallelic variants in PATL2 (OMIM: 614661), WEE2 (OMIM: 614084), PADI6 (OMIM: 610363), NLRP5 (OMIM: 609658), and NLRP2 (OMIM: 609364) have been identified as the causes of a spectrum of PEL phenotypes, including oocyte maturation arrest, fertilization failure, and early embryonic arrest (Xu et al, 2016; Chen et al, 2017; Sang et al, 2018; Mu et al, 2019). Variants in these genes can only explain a few cases, and the genetic basis of PEL is still largely unclear
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