TMEM232 is required for the formation of sperm flagellum and male fertility in mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1119455 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29263978_1.fastq.gz | Fastqsanger.gz | |||
| SRR29263978_2.fastq.gz | Fastqsanger.gz | |||
| SRR29263979_1.fastq.gz | Fastqsanger.gz | |||
| SRR29263979_2.fastq.gz | Fastqsanger.gz | |||
| SRR29263980_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:Asthenoteratozoospermia is a major cause of male infertility. Thus far, the identified related genes can explain only a small share of asthenoteratozoospermia cases, suggesting the involvement of other genes. The transmembrane protein TMEM232 is highly expressed in mouse testes. In the present study, to determine its function of TMEM232 in testes, we constructed a Tmem232-null mouse model using CRISPR–Cas9 technology. Tmem232 knockout (KO) male mice was completely infertile, and their sperm were immotile, with morphological defects of the flagellum. Electron microscopy revealed an aberrant midpiece-principal junction and the loss of the fourth of nine doublet microtubules in the sperm of Tmem232-/-mice. Sperm cells presented an 8+2 conformation and an irregular arrangement of the mitochondrial sheath. Proteomic analysis indicated a downregulation in the expression of proteins associated with flagellar motility, sperm capacitation, and the integrity and stability of sperm structure, as well as an upregulation in the expression of multiple ribosome components in TMEM232-deficient spermatids. Additionally, TMEM232 was observed to be involved in ribophagy by interacting with autophagy-related proteins, such as ATG14 and ARMC3, to regulate ribosome homeostasis during spermiogenesis. These results suggest that TMEM232 is essential for normal sperm flagellum formation and plays an important role in the autophagic elimination of cytosolic ribosomes to provide energy for flagellar motility.
2024-06-06 | GSE268908 | GEO
Project description:For a sperm to successfully fertilize an egg, it must first undergo capacitation in the female reproductive tract, and later undergo acrosomal reaction (AR) upon encountering an egg. How premature AR is avoided despite rapid surges in signaling cascades during capacitation remains unknown. Using a combination of KO mice and cell-penetrating peptides, here we show that GIV (CCDC88A), a guanine nucleotide-exchange factor (GEM) for trimeric GTPases, is highly expressed in spermatocytes and is required for male fertility. GIV is rapidly phosphoregulated on key tyrosine and serine residues in human and murine sperms. These phosphomodifications enable GIV-GEM to orchestrate two distinct compartmentalized signaling programs in the sperm tail and head; in the tail, GIV enhances PI3K→Akt signals, sperm motility and survival, whereas in the head it inhibits cAMP surge and premature AR. Furthermore, GIV transcripts are downregulated in the testes and semen of infertile men. These findings exemplify the spatiotemporally segregated signaling programs that support sperm capacitation and the etiology of infertility in men.
2021-08-16 | GSE171704 | GEO
Project description:GIV/Girdin Regulates Spatiotemporal Signaling during Sperm Capacitation and is Required for Male Fertility
| PRJNA720623 | ENA
Project description:Primary objectives: To assess the impact of antiTNF agents on the male inflammatory bowel diseases patients` fertility
Primary outcomes:- semen quality and quantity, inclusive sperm chromatine structure analysis prior and during anti-TNF therapy- time to conception
| 2525194 | ecrin-mdr-crc
Project description:Despite passing routine laboratory tests for semen quality, bulls used in artificial insemination (AI) can exhibit a significant variation in fertility. During fertility analysis, a subfertile bull with a low pregnancy rate of 10% was identified. To fully characterize the phenotype, a range of in vitro, in vivo and molecular assays were carried out. Additionally, knockout mice were generated to investigate the function of the identified mutated gene. Sperm from the subfertile bull exhibited reduced motility and severely reduced caffeine-induced hyperactivation compared to control bulls of proven fertility. Ability to penetrate the zona pellucida, cleavage rate, cleavage kinetics, and blastocyst yield after IVF or AI were significantly lower than in control bulls. Whole-genome sequencing and RNA sequencing of testis revealed a critical mutation in AK9 that affect splicing, shaping the majority of AK9 transcripts that leads to a premature termination codon and a severely truncated protein. Transgenic mice deficient in AK9 were generated, resulting in the production of immotile sperm that were unable to fertilize the oocyte. These sperm exhibited abnormalities, including a low ATP concentration. RNA-seq analysis of testis revealed differential gene expression of components of the axoneme and sperm flagella, as well as steroid metabolic processes. Sperm ultrastructural analysis showed a higher percentage of sperm with abnormal flagella. The infertility produced by AK9 mutant bull and in AK9 deficient mice indicates the essential metabolic role of AK9 in sperm motility and/or hyperactivation, which in turn affects sperm binding and penetration of the zona pellucida.
2023-09-22 | GSE235546 | GEO
Project description:PurposeTRANSLIN (TSN) and its binding partner TSNAX have been reported to contribute to a wide spectrum of biological activities including spermatogenesis. TSN accompanies specific mRNA transport in male germ cells through intercellular bridges. A testis-expressed protein TSNAXIP1 was reported to interact with TSNAX. However the role of TSNAXIP1 in spermatogenesis remained unclear. This study aimed to elucidate the role of TSNAXIP1 in spermatogenesis and male fertility in mice.MethodsTSNAXIP1 knockout (KO) mice were generated using the CRISPR-Cas9 system. The fertility, spermatogenesis, and sperm of TSNAXIP1 KO males were analyzed.ResultsTSNAXIP1, and especially its domains, are highly conserved between mouse and human. Tsnaxip1 was expressed in testis, but not in ovary. TSNAXIP1 KO mice were generated, and TSNAXIP1 KO males were found to be sub-fertile with smaller testis and lower sperm count. Although no overt abnormalities were observed during spermatogenesis, lack of TSNAXIP1 induced sperm head malformation, resulting in a unique flower-shaped sperm head. Moreover, abnormal anchorage of the sperm neck was frequently observed in TSNAXIP1 null sperm.ConclusionA testis-expressed gene TSNAXIP1 has important roles in sperm head morphogenesis and male fertility. Moreover, TSNAXIP1 could be a causative gene for human infertility.
| S-EPMC10304756 | biostudies-literature
Project description:Spermatogenesis is a crucial biological process that enables the production of functional sperm, allowing for successful reproduction. Proper germ cell differentiation and maturation require tight regulation of hormonal signals, cellular signaling pathways, and cell biological processes. The acrosome is a lysosome-related organelle at the anterior of the sperm head that contains enzymes and receptors essential for egg-sperm recognition and fusion. Even though several factors crucial for acrosome biogenesis have been discovered, the precise molecular mechanism of pro-acrosomal vesicle formation and fusion is not known. In this study, we investigated the role of the insulin inhibitory receptor (inceptor) in acrosome formation. Inceptor is a single-pass transmembrane protein with similarities to mannose-6-phosphate receptors (M6PR). Inceptor knockout mice are infertile due to malformations in the acrosome and defects in the nuclear shape of spermatozoa. We show that inceptor is expressed in early spermatids and mainly localizes to vesicles between the Golgi apparatus and acrosome. We propose that inceptor is an important factor in the intracellular transport of trans-Golgi network (TGN)-derived clathrin-coated vesicles delivering acrosomal cargo in maturing spermatids, and its absence results in vesicle-fusion defects, acrosomal malformation, and male infertility. These findings support our hypothesis of inceptor as a universal lysosomal or lysosome-related organelle sorting receptor expressed in several secretory tissues.
2023-08-28 | PXD043946 | Pride
Project description:Purpose: Screening the sperm sncRNAs that are responsible for dairy cattle fertility is of great interest, however, exploring the fertility-associated sncRNAs in sperm and linking them with the epigenetic inheritance in bovine has not been performed yet. Here in this study, we hypothesized that some sncRNAs in bovine sperm have a great potential to be linked with direct and immediate bull fertility data and could later influence the embryo and possibly impacting the daughter fertility. Methods: 12 bovine cryopreserved semen (high bull fertility, n=3 VS low bull fertility, n=3; high daughter fertility, n=3 vs low daughter fertility, n=3) that came from a pre-filtered 100 bull list (Figure 1) had been selected to extract total sperm RNA, the somatic cell lysis buffer had been added during the RNA extraction process to avoid the somatic cell pollution. The maternal and other confounding factors had been taken into consideration during the calculation of the phenotype criteria index.After the library construction, the library size that was smaller than 200 base pairs (adapter size around 125 nt) had been cut and sent for next-generation sequencing Results: bull fertility and daughter fertility related sncRNAs had been identified. Conclusions: providing promising epigenetic biomarker for cattle fertility improvement in the future, although these small non-coding RNAs need to be validated in larger sample sizes before being used as biomarkers.
2024-02-16 | GSE225705 | GEO
Project description:The flagellum is an evolutionarily conserved appendage used for sensing and locomotion. Its backbone is the axoneme and a component of the axoneme is the radial spoke (RS), a protein complex implicated in flagellar motility regulation. Numerous diseases occur if the axoneme is improperly formed, such as primary ciliary dyskinesia (PCD) and infertility. Radial spoke head 6 homolog A (RSPH6A) is an ortholog of Chlamydomonas RSP6 in the RS head and is evolutionarily conserved. While some RS head proteins have been linked to PCD, little is known about RSPH6A. Here, we show that mouse RSPH6A is testis-enriched and localized in the flagellum. Rsph6a knockout (KO) male mice are infertile as a result of their short immotile spermatozoa. Observation of the KO testis indicates that the axoneme can elongate but is disrupted before accessory structures are formed. Manchette removal is also impaired in the KO testis. Further, RSPH9, another radial spoke protein, disappeared in the Rsph6a KO flagella. These data indicate that RSPH6A is essential for sperm flagellar assembly and male fertility in mice.This article has an associated First Person interview with the first author of the paper.
| S-EPMC6198453 | biostudies-literature
Project description: In sexually reproducing organisms, sperm contribute half the genomic material required for creation of offspring and natural fertility relies on males producing millions by way of spermatogenesis. This process is essential for continuity and diversity of a species, yet evolutionarily conserved core molecular regulators are undefined. Here we used single cell RNA-sequencing of testicular tissue from mice, pigs, and cattle to generate a multispecies integrated transcriptome database. Through bioinformatic analysis, the gene arrestin-domain containing 5 (Arrdc5) which encodes for an α-arrestin molecule was identified as a potential evolutionarily conserved regulator of spermatogenesis. Expression of Arrdc5 is testis specific in mice, pigs, cattle, and humans. Knockout of Arrdc5 in mice leads to male specific sterility due to production of low numbers of sperm that are immotile and malformed, resembling oligoasthenoteratospermia (OAT) which is a common diagnosis of infertility in men. Spermiogenesis, the final phase of spermatogenesis when round spermatids morphologically transform to spermatozoa, is defective in testes of Arrdc5 deficient mice. Also, epididymal sperm in Arrdc5 knockouts are unable to capacitate and fertilize oocytes. These findings establish Arrdc5 as a core regulator of mammalian spermatogenesis. Considering the role of arrestin molecules as modulators of G-protein coupled signaling and ubiquitination, Arrdc5 is a potential male contraceptive target.
2023-03-06 | GSE206156 | GEO