Germline-specific deletion of testis-highly expressed Lrwd1 reveals nonessential roles in male fertility

Genetic etiologies constitute a major contributor to male factor infertility, a global health concern impacting over 7% of the reproductive-aged male population. Comprehensive transcriptomic profiling has identified more than 2300 mouse testicular-predominant genes, with knockout models functionally validating the critical role of numerous loci in preserving fertility. However, the biological significance of large portions of the male germ cell genes remains unclear. The present study aimed to investigate the function of leucine-rich repeats and WD40 repeat domain-containing protein 1 (Lrwd1) in male reproduction. Here we generated germ cell-specific Lrwd1 knockout mice with Stra8-Cre (Lrwd1-sKO) using CRISPR/Cas9 technology and assessed their fertility. Our results demonstrated that the absence of Lrwd1 did not affect the fertility of male mice, and no significant differences in sperm morphology were observed between Lrwd1-sKO and control mice. Histological analysis of testicular and epididymal tissues revealed that seminiferous tubules contained all stages of germ cell development, including mature spermatozoa, without noticeable alterations. Additionally, the progression of spermatocytes through prophase I was not impaired in ablation of Lrwd1 in germ cell. These findings suggest that Lrwd1 is not essential for spermatogenesis or male fertility in mice, indicating that it does not play a critical role in reproductive function under normal physiological conditions.