Novel Genes of the Male Reproductive System: Potential Roles in Male Reproduction and as Non‐hormonal Male Contraceptive Targets

Molecular Reproduction and Development, Journal Year: 2024, Volume and Issue: 91(10)

Published: Oct. 1, 2024

ABSTRACT The development of novel non‐hormonal male contraceptives represents a pivotal frontier in reproductive health, driven by the need for safe, effective, and reversible contraceptive methods. This comprehensive review explores genetic underpinnings fertility, emphasizing crucial roles specific genes structural variants (SVs) identified through advanced sequencing technologies such as long‐read (LRS). LRS has revolutionized detection complex genomic regions, offering unprecedented precision resolution over traditional next‐generation (NGS). Key targets, including those implicated spermatogenesis sperm motility, are highlighted, showcasing their potential targets. delves into systematic identification validation tract‐specific genes, utilizing transcriptomics genomics studies with using knockout mouse models. We discuss innovative application small molecule inhibitors, developed platforms like DNA‐encoded chemistry technology (DEC‐Tec), which have shown significant promise preclinical Notable examples include inhibitors targeting serine/threonine kinase 33 (STK33), soluble adenylyl cyclase (sAC), cyclin‐dependent 2 (CDK2), bromodomain testis associated (BRDT), each demonstrating nanomolar affinity inhibition fertility. also honors contributions Dr. David L. Garbers whose foundational work paved way these advancements. integration genomic, proteomic, chemical biology approaches, supported interdisciplinary collaboration, is poised to transform development. Future perspectives emphasize continued innovation rigorous testing bring from laboratory clinical application, promising new era health management.

Language: Английский

The Sperm‐Associated Antigen 11A (Spag11a) Knockout Mice Display Sub‐Fertility and Perturbations in the Sperm Proteome

Cell Biochemistry and Function, Journal Year: 2024, Volume and Issue: 42(7)

Published: Oct. 1, 2024

Spermatogenesis and sperm maturation that occur in the testis epididymis respectively are crucial for fertility. Factors secreted by testicular epididymal epithelial cells govern processes of gametogenesis maturation. Proteins encoded sperm-associated antigen 11a (Spag11a) gene implicated as having a possible role However, studies demonstrate their definite fertility function using knockout models have not yet reported. In this study, Spag11a mice were generated, genotyped reproductive parameters (fecundity, count, capacitation, acrosome reaction) proteome determined. Litter size count decreased when compared to wild-type controls. Spermatozoa from able undergo capacitation. reaction did obtained mice. Structural abnormalities head tail structures evident spermatozoa Perturbations expression proteins involved evident. The subfertility observed could be manifestation lower impaired reactions, disturbances proteome. results study lend further support male gamete function.

Language: Английский