Volume 31, No 7, Jul 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 7, July 2021: 814-817   |  Open Access

LETTERS TO THE EDITOR

Dominant mutations in CHK1 cause pronuclear fusion failure and zygote arrest that can be rescued by CHK1 inhibitor

Honghui Zhang^1,2,3,4 , Tailai Chen^5,6 , Keliang Wu^1,2,3,4 , Zhenzhen Hou^1,2,3,4 , Shigang Zhao^1,2,3,4 , Chuanxin Zhang^1,2,3,4 , Yuan Gao^1,2,3,4 , Ming Gao^1,2,3,4 , Zi-Jiang Chen^{1,2,3,4,5,6,*} , Han Zhao^1,2,3,4,*

¹Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
²National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China
³Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China
⁴Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, Shandong, China
⁵Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
⁶Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
These authors contributed equally: Honghui Zhang, Tailai Chen, Keliang Wu, Zhenzhen Hou Correspondence: Zi-Jiang Chen(chenzijiang@hotmail.com)Han Zhao(hanzh80@sdu.edu.cn)

Dear Editor,

Infertility poses a major challenge to human reproductive health, affecting approximately 48 million women worldwide.1 Assisted reproductive techniques (ART), including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), enable infertile women to have their biological embryos in vitro and further give birth to babies after embryo transfer. However, about 10% of all human embryos produced by ART are blocked in the early embryonic stage2 and approximately 2% fertilized oocytes derived from ART could not accomplish the first cell division.3 About one half of human infertility cases involve an underlying genetic factor, although the majority of genetic causes have remained elusive.4 In this study, we report that dominant mutations in CHK1 are responsible for pronuclear fusion failure and zygote arrest (PFF-ZA) in 7 out of 29 cases, likely through increasing the CHK1 activity. Importantly, PFF-ZA caused by these mutations could be effectively rescued by using the CHK1 inhibitor, PF477736.

https://doi.org/10.1038/s41422-021-00507-8

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