Embryonic MTHFR contributes to blastocyst development
H Ishitani, S Ikeda, K Egashira, M Sugimoto… - Journal of Assisted …, 2020 - Springer
H Ishitani, S Ikeda, K Egashira, M Sugimoto, S Kume, N Minami, T Ohta
Journal of Assisted Reproduction and Genetics, 2020•SpringerPurpose Reduction in methylenetetrahydrofolate reductase (MTHFR) activity due to genetic
variations in the MTHFR gene has been controversially implicated in subfertility in human in
vitro fertilization. However, there is no direct gene-knockdown study of embryonic MTHFR to
assess its involvement in mammalian preimplantation development. The purpose of this
study is to investigate expression profiles and functional roles of MTHFR in bovine
preimplantation development. Methods Reverse transcription-quantitative PCR (RT-qPCR) …
variations in the MTHFR gene has been controversially implicated in subfertility in human in
vitro fertilization. However, there is no direct gene-knockdown study of embryonic MTHFR to
assess its involvement in mammalian preimplantation development. The purpose of this
study is to investigate expression profiles and functional roles of MTHFR in bovine
preimplantation development. Methods Reverse transcription-quantitative PCR (RT-qPCR) …
Purpose
Reduction in methylenetetrahydrofolate reductase (MTHFR) activity due to genetic variations in the MTHFR gene has been controversially implicated in subfertility in human in vitro fertilization. However, there is no direct gene-knockdown study of embryonic MTHFR to assess its involvement in mammalian preimplantation development. The purpose of this study is to investigate expression profiles and functional roles of MTHFR in bovine preimplantation development.
Methods
Reverse transcription-quantitative PCR (RT-qPCR) and analysis of publicly available RNA-seq data were performed to reveal expression levels of MTHFR during bovine preimplantation development. We knocked down MTHFR by siRNA-mediated RNA interference from the 8- to 16-cell stage and assessed the effects on preimplantation development.
Results
The RT-qPCR analysis showed relatively high MTHFR expression at the GV oocyte stage, which was decreased toward the 8- to 16-cell stage and then slightly restored at the blastocyst stage. Public data–based analysis also showed the similar pattern of expression with substantial embryonic expression at the blastocyst stage. MTHFR knockdown reduced the blastocyst rate (P < 0.01) and the numbers of total (P < 0.0001), trophectoderm (P < 0.0001), and inner cell mass (P < 0.001) cells.
Conclusion
The results indicate that embryonic MTHFR is indispensable for normal blastocyst development. The findings provide insight into the debatable roles of MTHFR in fertility and may be applicable for the improvement of care for early embryos via modulation of surrounding folate-related nutritional conditions in vitro and/or in utero, depending on the parental and embryonic MTHFR genotype.
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