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Spermatozoa need to undergo an exocytotic event called the acrosome reaction before fusing with eggs. Although calcium ion (Ca) is essential for the acrosome reaction, its molecular mechanism remains unknown. Ferlin is a single transmembrane protein with multiple Ca-binding C2 domains, and there are six ferlins, dysferlin (DYSF), otoferlin (OTOF), myoferlin (MYOF), fer-1-like 4 (FER1L4), FER1L5, and FER1L6, in mammals. , , and knockout mice have been generated, and each knockout mouse line exhibited membrane fusion disorders such as muscular dystrophy in , deafness in , and abnormal myogenesis in . Here, by generating mutant mice of , , and , we found that only is required for male fertility. mutant spermatozoa could migrate in the female reproductive tract and reach eggs, but no acrosome reaction took place. Even a Ca ionophore cannot induce the acrosome reaction in mutant spermatozoa. These results suggest that FER1L5 is the missing link between Ca and the acrosome reaction.
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http://dx.doi.org/10.1126/sciadv.ade7607 | DOI Listing |
Cryobiology
September 2025
Laboratory of Teaching and Research in Pathology of Reproduction, Center of Biotechnology in Animal Reproduction, Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, University of São Paulo (USP), Pirassununga, SP, Brazil. Electronic address:
Sperm capacitation is a critical process for successful fertilization, involving multiple regulated cellular changes. On the other hand, cryopreservation induces membrane changes that can mimic capacitation, potentially leading to misinterpretation of sperm function. Distinguishing true capacitation from cryoinjury remains challenging, as both share surface markers despite involving distinct mechanisms and impacts on fertilization.
View Article and Find Full Text PDFFront Vet Sci
August 2025
Department of Internal Medicine, Reproduction and Population Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Nano-sized extracellular vesicles (EVs) possess a lipid bilayer and are secreted from cells into their surrounding environment. The transport of multiple biomolecules, including DNA together with RNA, microRNAs (miRNAs), lipids, proteins, and metabolites, happens through biofluids via EVs for intercellular communication. Extracellular vesicles play crucial roles during the embryo production (IVEP) process.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Department of Advanced Medical Technologies, National Cerebral and Cardiovascular Center, Suita, Osaka 564-8565, Japan.
In mammals, sperm formation is completed in the seminiferous tubules within the testis, and sperm maturation occurs during the epididymal transit of the spermatozoa. Sperm morphology drastically changes when abnormal spermatozoa migrate from the testis to the epididymis. Detailed molecular mechanisms for sperm survival in the epididymis have not been determined yet.
View Article and Find Full Text PDFBiology (Basel)
August 2025
Department of Agricultural, Food and Environmental Sciences, University of Perugia, 06121 Perugia, Italy.
The aim of this study was to analyze how recombinant rabbit NGF (Nerve Growth Factor) encapsulated in chitosan (rrβNGFch) affects sperm viability, motility, capacitation, acrosome reaction (AR), kinetic traits, and apoptosis after 30 min and 2 h of storage. Specific intracellular signaling pathways associated with either cell survival, such as protein kinase B (AKT) and extracellular signal-regulated kinases 1/2 (ERK1/2), or programmed cell death, such as c-Jun N-terminal kinase (JNK), were also analyzed. The results confirmed the effect of rrβNGFch on capacitation and AR, whereas a longer storage time (2 h) decreased all qualitative sperm traits.
View Article and Find Full Text PDFJ Poult Sci
August 2025
Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan.
Sperm-egg interactions involve a complex series of molecular events. Among these, the acrosome reaction (AR) is a prerequisite for sperm penetration, facilitating the exposure of multiple acrosomal proteins that enhance sperm binding or penetration of the outer layer of the egg; however, the specific molecules involved in this process vary across species. A disintegrin and metalloproteinase (ADAM) proteins are transmembrane glycoproteins that play a role in sperm-egg interactions, with notable differences among ADAM isoforms.
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