SEPT14 complexes maintain sperm morphogenesis and function

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(4)

Published: Feb. 21, 2025

Abstract Mutations in the septin (SEPT) family lead to male infertility. Septin 14 (SEPT14) is abundantly expressed testis, and its expression significantly reduced individuals with teratozoospermia, suggesting that SEPT14 may play a role spermatogenesis. Here, we demonstrated Sept14 mainly at acroplaxome, manchette, neck, annulus during spermiogenesis. To study of sperm morphogenesis function, knockout ( −/− ) mice were generated. The subfertile presented phenotypes such as irregular acrosomes, DNA damage, disorganized mitochondria, displaced annuli. These abnormalities contributed motility impaired capacitation. Mechanistically, head, interacted colocalized microtubules actin manchette formation metamorphosis phase. In annulus, SEPT9, SEPT7, SEPT2 form filaments maintain localization annulus. GTP‐binding domain (GBD) GBD SEPT2, whereas C‐terminus SEPT7. Thus, our reveals mediating morphogenesis.

Language: Английский

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