CRISPR/Cas9 in Male Factor Infertility

Male factor infertility is common and often multifactorial. A subset of these patients have underlying genetic etiologies. CRISPR/Cas9 is a simple and flexible gene editing tool with promising applications in this space. This review aims to summarize the advances that CRISPR/Cas9-based tools have brought to the field and propose future directions for study. CRISPR/Cas9 has been applied successfully to spermatogonial stem cells (SSCs) and via pronuclear injection of zygotes to generate animal models of male factor infertility. These approaches have led to the high-throughput validation of candidate male fertility genes obtained either through genome-wide associated studies or testis-specific gene expression studies. One group has applied this further to SSCs in the correction of genetic infertility due to a mutation in the Kit gene. Application of CRISPR/Cas9 to the investigation and treatment of male infertility holds promise in identifying novel genetic causes of NOA. Gene editing in germ cells to treat genetic infertility is technically feasible, but has not been used in humans due to significant ethical concerns. Stringent regulations are imperative to ensure safe translation of this technology into human populations.