Novel Homozygous PADI6 Variants in Infertile Females with Early Embryonic Arrest

Yao Xu; Rongxiang Wang; Zhi Pang; Zhiyun Wei; Lihua Sun; Sa Li; Guanghua Wang; Yu Liu; Yiwen Zhou; Hongjuan Ye; Liping Jin; Songguo Xue

doi:10.3389/fcell.2022.819667

Novel Homozygous PADI6 Variants in Infertile Females with Early Embryonic Arrest

Front Cell Dev Biol. 2022 Apr 1:10:819667. doi: 10.3389/fcell.2022.819667. eCollection 2022.

Authors

Yao Xu¹, Rongxiang Wang², Zhi Pang³, Zhiyun Wei¹, Lihua Sun², Sa Li⁴, Guanghua Wang¹, Yu Liu², Yiwen Zhou², Hongjuan Ye², Liping Jin¹, Songguo Xue²

Affiliations

¹ Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
² Reproductive Medicine Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
³ Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China.
⁴ Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Beijing, China.

Abstract

Early embryonic arrest denotes premature termination of development in preimplantation embryos, which is one of the major phenotypes of recurrent assisted reproduction failure. Padi6 is proven to be a member of the subcortical maternal complex (SCMC) in mice, which is essential in oocyte maturation and embryogenesis. We and other groups previously found that biallelic mutations in PADI6 caused female infertility manifesting as early embryonic arrest. In this study, we identified two novel homozygous variants (p.Cys163Arg, and p. Trp475*) of PADI6 in two infertile patients from a cohort of 75 females with the phenotype of early embryonic arrest. An in vitro expression study indicated severe decrease of PADI6, which might destruct the stability of SCMC. Our study expands the mutational spectrum of PADI6 and further supports the causality between PADI6 mutations and female infertility.

Keywords: PADI6; early embryonic arrest; female infertility; novel variant; subcortical maternal complex.