Rescue of Male Infertility Through Correcting a Genetic Mutation Causing Meiotic Arrest in Spermatogonial Stem Cells

Overview

Journal Asian J Androl

Specialty Urology

Date 2021 Feb 3

PMID 33533741

Citations 17

Authors

Ying-Hua Wang

Meng Yan

Xi Zhang

Xin-Yu Liu

Yi-Fu Ding

Chong-Ping Lai

Ming-Han Tong

Jin-Song Li

Affiliations

Soon will be listed here.

Abstract

Azoospermia patients who carry a monogenetic mutation that causes meiotic arrest may have their biological child through genetic correction in spermatogonial stem cells (SSCs). However, such therapy for infertility has not been experimentally investigated yet. In this study, a mouse model with an X-linked testis-expressed 11 (TEX11) mutation (Tex11) identified in azoospermia patients exhibited meiotic arrest due to aberrant chromosome segregation. Tex11 SSCs could be isolated and expanded in vitro normally, and the mutation was corrected by clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated endonuclease 9 (Cas9), leading to the generation of repaired SSC lines. Whole-genome sequencing demonstrated that the mutation rate in repaired SSCs is comparable with that of autonomous mutation in untreated Tex11 SSCs, and no predicted off-target sites are modified. Repaired SSCs could restore spermatogenesis in infertile males and give rise to fertile offspring at a high efficiency. In summary, our study establishes a paradigm for the treatment of male azoospermia by combining in vitro expansion of SSCs and gene therapy.

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