FBXO24 deletion causes abnormal accumulation of membraneless electron-dense granules in sperm flagella and male infertility DOI Creative Commons
Yuki Kaneda, Haruhiko Miyata,

Zoulan Xu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 10, 2023

Abstract Ribonucleoprotein (RNP) granules are membraneless electron-dense structures rich in RNAs and proteins, involved various cellular processes. Two RNP male germ cells, intermitochondrial cement the chromatoid body (CB), associated with PIWI-interacting (piRNAs) required for transposon silencing spermatogenesis. Other reticulated CB remnants, also essential spermiogenesis. In this study, we disrupted FBXO24, a testis-enriched F-box protein, mice found numerous accumulated sperm flagella. Fbxo24 knockout (KO) exhibited malformed flagellar structures, impaired motility, infertility, likely due to accumulation of abnormal granules. The amount localization known granule-related proteins were not KO mice, suggesting that distinct from Further studies revealed two importins, IPO5 KPNB1, abnormally spermatozoa FBXO24 could ubiquitinate IPO5. addition, KPNB1 recruited stress granules, complexes, when cells treated oxidative or proteasome inhibitor. These results suggest is degradation IPO5, disruption which may lead

Language: Английский

Development of functional spermatozoa in mammalian spermiogenesis DOI
Haruhiko Miyata, Keisuke Shimada, Yuki Kaneda

et al.

Development, Journal Year: 2024, Volume and Issue: 151(14)

Published: July 15, 2024

ABSTRACT Infertility is a global health problem affecting one in six couples, with 50% of cases attributed to male infertility. Spermatozoa are gametes, specialized cells that can be divided into two parts: the head and flagellum. The contains vesicle called acrosome undergoes exocytosis flagellum motility apparatus propels spermatozoa forward components, axonemes accessory structures. For fertilize oocytes, must formed correctly. In this Review, we describe comprehensively how functional develop mammals during spermiogenesis, including formation acrosomes, structures by focusing on analyses mouse models.

Language: Английский

Citations

10
MAPKs signaling is obligatory for male reproductive function in a development-specific manner DOI Creative Commons
Lokesh Kumar,

Subhash Solanki,

Ashish Jain

et al.

Frontiers in Reproductive Health, Journal Year: 2024, Volume and Issue: 6

Published: Feb. 9, 2024

Mitogen-activated protein kinases (MAPKs) represent widely expressed and evolutionarily conserved proteins crucial for governing signaling pathways playing essential roles in mammalian male reproductive processes. These facilitate the transmission of signals through phosphorylation cascades, regulating diverse intracellular functions encompassing germ cell development testis, physiological maturation spermatozoa within epididymis, motility regulation at ejaculation female tract. The conservation these mechanisms appears prevalent across species, including humans, mice, and, to a limited extent, livestock species such as bovines. In Sertoli cells (SCs), MAPK not only regulates proliferation immature SCs but also determines appropriate number testes puberty, thereby maintaining fertility by ensuring capacity sperm production. cells, MAPKs play role dynamically testicular cell-cell junctions, supporting differentiation. Throughout spermatogenesis, ensures Sertoli-to-germ ratio apoptosis, controlling metabolism developing facilitating cauda epididymis. During tract, regulate two pivotal events—capacitation acrosome reaction potential cells. Any disruptions pathway possibly may disturb microenvironment homeostasis, physiology body before tract during fertilization, ultimately compromising fertility. Despite decades research, function health remains inadequately understood. current review attempts combine recent findings elucidate impact on proposes future directions enhance our understanding functions.

Language: Английский

Citations

4
The Various Mechanisms by Which Exercise-Induced Fatigue (EIF) Affects Spermatogenesis Through Testosterone DOI

Kun-Yang Tang,

Zhipeng Fang, Min Xiao

et al.

Reproductive Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Language: Английский

Citations

0
Zinc mitigates cadmium-induced sperm dysfunction through regulating Ca2+ and metallothionein expression in the freshwater crab Sinopotamon henanense DOI
Jing Liu,

Ermeng Wang,

Zhipeng Xi

et al.

Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology, Journal Year: 2024, Volume and Issue: 279, P. 109860 - 109860

Published: Feb. 20, 2024

Language: Английский

Citations

3
Membrane potential hyperpolarization: a critical factor in acrosomal exocytosis and fertilization in sperm within the female reproductive tract DOI Creative Commons
Paula A. Balestrini,

Valeria Sulzyk,

Martina Jabloñski

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: May 13, 2024

Hyperpolarization of the membrane potential (Em), a phenomenon regulated by SLO3 channels, stands as central feature in sperm capacitation—a crucial process conferring upon ability to fertilize oocyte. In vitro studies demonstrated that Em hyperpolarization plays pivotal role facilitating mechanisms necessary for development hyperactivated motility (HA) and acrosomal exocytosis (AE) occurrence. Nevertheless, physiological significance within female reproductive tract remains unexplored. As an approach this question, we studied migration AE incidence oviduct absence using novel mouse model established crossbreeding knock-out (KO) mice with EGFP/DsRed2 mice. Sperm from displays impaired HA . Interestingly, examination shows KO can reach ampulla , mirroring quantity observed wild-type (WT) counterparts, supporting needed fertilization site is not affected. However, noteworthy distinction emerges—unlike WT sperm, majority arrive at their acrosomes still intact. Of few do manage oocytes location, does occur, indicated pronuclei MII-oocytes recovered post-mating. fail penetrate ZP fuse oocytes. Collectively, these results underscore vital context, while also revealing prerequisite motility, essential through

Language: Английский

Citations

3
Golgi associated RAB2 interactor protein family contributes to murine male fertility to various extents by assuring correct morphogenesis of sperm heads DOI Creative Commons
Haoting Wang, Rie Iida‐Norita, Daisuke Mashiko

et al.

PLoS Genetics, Journal Year: 2024, Volume and Issue: 20(6), P. e1011337 - e1011337

Published: June 27, 2024

Sperm heads contain not only the nucleus but also acrosome which is a distinctive cap-like structure located anterior to and derived from Golgi apparatus. The Associated RAB2 Interactors (GARINs; known as FAM71) protein family shows predominant expression in testis all possess RAB2-binding domain confers binding affinity RAB2, small GTPase that responsible for membrane transport vesicle trafficking. Our previous study showed GARIN1A GARIN1B are important biogenesis indispensable male fertility mice. Here, we generated KO mice of other Garins , namely Garin2 Garin3 Garin4 Garin5a Garin5b ( Garin2-5b ). Using computer-assisted morphological analysis, found loss each resulted aberrant sperm head morphogenesis. While fertilities -/- males normal, subfertile, infertile. Further analysis revealed exhibited abnormal acrosomal morphology, severely Garin1b males; instead, amounts proteins, particularly ADAM decreased spermatozoa. Moreover, exhibit vacuoles head. These results indicate GARINs assure correct morphogenesis some members GARIN function distinctively fertility.

Language: Английский

Citations

3
Spermatogenic cell-specific type 1 hexokinase (HK1S) is essential for capacitation-associated increase in tyrosine phosphorylation and male fertility in mice DOI Creative Commons

Yingchao Tian,

Xiu Chen,

Jie Pu

et al.

PLoS Genetics, Journal Year: 2024, Volume and Issue: 20(7), P. e1011357 - e1011357

Published: July 29, 2024

Hexokinase (HK) catalyzes the first irreversible rate-limiting step in glycolysis that converts glucose to glucose-6-phosphate. HK1 is ubiquitously expressed brain, erythrocytes, and other tissues where serves as major source of ATP production. Spermatogenic cell-specific type 1 hexokinase (HK1S) sperm but its physiological role male mice still unknown. In this study, we generate Hk1s knockout using CRISPR/Cas9 system study gene function vivo . mRNA exclusively testes starting from postnatal day 18 continuing adulthood. HK1S protein specifically localized outer surface fibrous sheath (FS). Depletion leads infertility reduces glycolytic pathway activity, yet they have normal motile parameters levels. addition, by vitro fertilization (IVF), deficient sperms are unable fertilize cumulus-intact or cumulus-free oocytes, can normally zona pellucida-free oocytes. Moreover, deficiency impairs migration into oviduct, acrosome reaction, prevents capacitation-associated increases tyrosine phosphorylation, which probable causes infertility. Taken together, our results reveal plays a critical fertility mice.

Language: Английский

Citations

3
Molecular mechanisms of mammalian sperm capacitation, and its regulation by sodium‐dependent secondary active transporters DOI Creative Commons
Gen L. Takei

Reproductive Medicine and Biology, Journal Year: 2024, Volume and Issue: 23(1)

Published: Jan. 1, 2024

Mammalian spermatozoa have to be "capacitated" fertilization-competent. Capacitation is a collective term for the physiological and biochemical changes in that occur within female body. However, regulatory mechanisms underlying capacitation not been fully elucidated.

Language: Английский

Citations

3
Complements from the Male Reproductive Tract: A Scoping Review DOI Creative Commons
Rachel L. Washburn

BioMed, Journal Year: 2024, Volume and Issue: 4(1), P. 19 - 38

Published: Jan. 25, 2024

The organs of the male reproductive tract, including testis, epididymis, prostate, seminal vesicles, and semen, must provide an immunoregulatory environment conducive to germ cell viability successful fertilization. Many immune components, such as cells, have been investigated regarding immunology function; however, investigation role complement in this system has only more recently gaining traction research. This review focuses on with goal compiling information currently known about components detected identifying areas need further Considering recent upcoming research noncanonical functions complement, is relevant applicable fields immunology, fertility, regulation.

Language: Английский

Citations

2
MYCBPAP is a central apparatus protein required for centrosome-nuclear envelope docking and sperm tail biogenesis in mice DOI Creative Commons
Haoting Wang, Hiroko Kobayashi, Keisuke Shimada

et al.

Journal of Cell Science, Journal Year: 2024, Volume and Issue: 137(16)

Published: Aug. 15, 2024

ABSTRACT The structure of the sperm flagellar axoneme is highly conserved across species and serves essential function generating motility to facilitate meeting spermatozoa with egg. During spermiogenesis, elongates from centrosome, subsequently centrosome docks onto nuclear envelope continue tail biogenesis. Mycbpap expressed predominantly in mouse human testes Chlamydomonas as FAP147. A previous cryo-electron microscopy analysis has revealed localization FAP147 central apparatus axoneme. Here, we generated Mycbpap-knockout mice demonstrated role male fertility. Deletion led disrupted centrosome–nuclear docking abnormal Furthermore, transgenic tagged MYCBPAP, which restored fertility males. Interactome analyses MYCBPAP using unveiled binding partners including proteins, such CFAP65 CFAP70, constitute C2a projection, centrosome-associated CCP110. These findings provide insights into a MYCBPAP-dependent regulation

Language: Английский

Citations

2