Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Fam170a deficiency causes male infertility by impairing histone-to-protamine exchange during mouse spermiogenesis

ABSTRACT: Families with sequence similarity 170 members A (Fam170a) deficiency caused abnormal sperm nuclear morphology and male infertility in mice, mirroring the observation of very low Fam170a transcription in sperm of infertile men with teratozoospermia.Fam170a directly interacted with the deubiquitinating enzyme Usp7 and promoted nuclear translocation of Usp7 in elongating sperm by its nuclear localization sequence, enhancing the deubiquitinating activity of Usp7 on testis-specific histone H2A and H2B variants. Collectively, our findings identified Fam170a as a previously unknown key regulator for sperm chromatin remodeling and revealed that histone deubiquitinating modification might also exert an essential role in the histone-to-protamine exchange.

ORGANISM(S): Mus Musculus

SUBMITTER: Fei Sun

PROVIDER: PXD057721 | iProX | Sun Nov 10 00:00:00 GMT 2024

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Publications

Fam170a deficiency causes male infertility by impairing histone-to-protamine exchange during mouse spermiogenesis.

Cheng Jinmei J Gu Yimin Y Wang Yueming Y Xun Junjie J Wang Guishuan G Wang Yu Y Wang Jianyu J Li Yinchuan Y Sun Fei F

Nucleic acids research 20250101 3

Chromatin remodeling, which involves the histone-to-protamine exchange process during spermiogenesis, is crucial for sperm nuclear condensation and male fertility. However, the key regulators and underlying molecular mechanisms involved in this process remain largely unexplored. In this study, we discovered that deficiency in the family with sequence similarity 170 member A (Fam170a) led to abnormal sperm nuclear morphology and male infertility in mice, mirroring the observation of very low Fam1 ...[more]

PMID: 39868537

Similar Datasets

Fam170a deficiency causes male infertility

Project description:During spermiogenesis, nucleus condensation packages genomic DNA into tiny sperm heads by histone-to-protamine chromatin remodeling process, which is essential to male fertility. However, this process involving key events and regulators is still poorly understood. Herein, we report that Fam170a orchestrates the histone-to-protamine chromatin remodeling process by interacting with its associated proteins and mediating its associated gene expression.

2024-11-10 | GSE280742 | GEO

Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella

Project description:Aberrant sperm flagella impair sperm motility and cause male infertility, yet the genes which have been identified in multiple morphological abnormalities of the flagella (MMAF) can only explain the pathogenic mechanisms of MMAF in a small number of cases. Here, we identify and functionally characterize homozygous loss-of-function mutations of QRICH2 in two infertile males with MMAF from two consanguineous families. Remarkably, Qrich2 knock-out (KO) male mice constructed by CRISPR-Cas9 technology present MMAF phenotypes and sterility. To elucidate the mechanisms of Qrich2 functioning in sperm flagellar formation, we perform proteomic analysis on the testes of KO and wild-type mice. Furthermore, in vitro experiments indicate that QRICH2 is involved in sperm flagellar development through stabilizing and enhancing the expression of proteins related to flagellar development. Our findings strongly suggest that the genetic mutations of human QRICH2 can lead to male infertility with MMAF and that QRICH2 is essential for sperm flagellar formation.

2019-11-12 | PXD011730 | Pride

Cross-sectional study of human spermatozoa mRNA from infertility study participants and proven-fertile control participants

Project description:The goal of this study was to identify mRNAs in spermatozoa that differ between idiopathic infertile men and proven-fertile men. The rationale is that there are many idiopathic infertile or subfertile men, and that semen parameters cannot reliably distinguish idopathic infertile men from fertile men. Spermatozoa contain thousands of RNAs, and the levels of those RNAs may reflect the extent of normal spermatogenesis and sperm maturation. We hypothesized that we could identify differences between two patient populations that would reflect their clinical fertility status.

2025-01-16 | GSE281732 | GEO

Importin α7 deficiency causes infertility in male mice by disrupting spermatogenesis

Project description:Spermatogenesis, a fundamental process in male reproduction, is driven by an ordered series of events, which rely on the trafficking of specific proteins between nucleus and cytoplasm. The importin α family of proteins mediates movement of specific cargo proteins when bound to importin β. Importin α genes have distinct expression patterns in mouse testis, implying they may have unique roles during mammalian spermatogenesis. Here we use a loss-of-function approach to specifically determine the role of importin α7 (Kpna6) in spermatogenesis and male fertility. We show that ablation of importin α7 in male mice leads to infertility and has multiple cumulative effects on both germ cells and Sertoli cells culminating in oligozoospermia. Importin α7-deficient mice exhibit an impaired Sertoli cell function, including loss of Sertoli cells from the seminiferous epithelium and a compromised nuclear transport of the androgen receptor. Furthermore, our data demonstrate devastating defects in spermiogenesis that are accompanied by a disturbed histone-protamine-exchange in elongating spermatids, resulting in incomplete sperm maturation and a massive loss of sperms. Our work uncovers the essential role of importin α7 in spermatogenesis and hence in male fertility.

2021-09-20 | GSE160969 | GEO

Sperm DNA Methylation Epimutation Biomarkers for Male Infertility and FSH Therapeutic Responsiveness

Project description:Male factor infertility is increasing and recognized as playing a key role in reproductive health and disease. The current primary diagnostic approach is to assess sperm quality associated with reduced sperm number and motility, which has been historically of limited success in separating fertile from infertile males. The current study was designed to develop a molecular analysis to identify male infertility using genome wide alterations in sperm DNA methylation. A signature of differential DNA methylation regions (DMRs) was identified to be associated with male infertility patients. A promising therapeutic treatment of male infertility is the use of follicle stimulating hormone (FSH) analogs which improved sperm numbers and motility in a sub-population of infertility patients. The current study also identified genome-wide DMRs that were associated with the patients that were responsive to FSH therapy versus those that were non-responsive.

2019-11-11 | GSE135825 | GEO

New insights on sperm function in male infertility of unknown origin: proteomics characterization

Project description:The global trend on (male)infertility is concerning and the unidentifiable causes in half of the cases demands a better understanding of the molecular, biochemical and metabolic mechanisms as well as the identification of external and internal factors operating behind it, that might help to explain this apparently unjustified infertility. This can only be achieved through a comprehensive analysis of the infertile men, in which external (lifestyle, occupational and environmental factors) and internal factors (psychological distress) should also be evaluated and considered, but also assessing sperm function beyond the routine seminal analysis. In this prospective cohort study, 79 sperm samples, from men who were male partners in couples seeking for infertility treatment, were collected at the Reproductive Medicine Unit (CHUC) from July 2018 to July 2022 and analyzed by SWATH-MS. Based on couples’ clinical data, seminal/hormonal analysis, and strict exclusion criteria, samples were categorized in the different groups, namely control (CTRL; 50 individuals), idiopathic infertile (ID; 19 patients) and unexplained infertile (UMI; 10 patients) men. In general, ID patients presented the worst sperm functional profile, while the UMI patients were observed to be similar to controls. These differences were also observed at the proteomics levels, which revealed 145 differentially expressed proteins (DEP) between the three groups, with more than 120 proteins being altered between ID and the other groups, and only 14 proteins were considered altered between CTRL and UMI.

2024-02-28 | PXD040292 | Pride

AK9 causes asthenozoospermia and male infertility

Project description:Deficiency in AK9 causes asthenozoospermia and male infertility by destabilizing sperm nucleotide homeostasis

2023-07-11 | PXD043689 |

Ejaculate samples for male infertility screening

Project description:The problem of the male reproductive system has both medical and social importance. It is highlighted that spermatozoa or seminal plasma are suitable samples for proteomic analysis of the male reproductive system. We suggested that the ejaculate could serve as one of the analytic specimens to determine fertility, which obtainable with relative ease and which contains many proteins. Moreover, the testis-specific proteins could form the basis of protein panel for detecting disorders associated with male infertility. The current study aimed to examine the ejaculate proteome compared to the spermatozoa and seminal plasma proteomes to determine a panel of proteins that can be used to assess sperm quality. Our results showed that the ejaculate represented a productive source for understanding the male reproductive physiology and could serve as a potential origin for the identification of novel protein biomarkers related to spermatozoa function in infertile. We believe that proteomic analysis based on testis-specific proteins of ejaculate along with spermatozoa (or even instead) can be useful for distinguishing the fertile, sub fertile, and infertile men.

2024-05-23 | PXD046848 | Pride

Tcte1 knockout influence on energy chain transportation, apoptosis and spermatogenesis – implications for male infertility

Project description:RNA sequencing (RNAseq) in testis tissue has been done to obtain an answer about the influence of Tcte1 null mutation in knockout mice on the expression pattern of other gonadal genes in male animals that may be influential for male fertility status. Homozygous males (infertile) revealed oligoasthenoteratozoospermia (incl. circular pathway of sperm motility), while heterozygous animals (fertile) manifested oligozoospermia, suggesting haploinsufficiency. RNA-sequencing of the mutant testicular tissue showed the influence of Tcte1 mutations on the expression pattern of genes responsible for mitochondrial ATP processing, linked with apoptosis, or spermatogenesis.

2023-02-01 | GSE207805 | GEO

Differential RNAs in the sperm cells of asthenozoospermic patients

Project description:Alterations in the presence of sperm RNAs have been identified using microarrays in teratozoospermic (abnormal morphology) or other types of infertile patients. However, so far no studies had been reported on the sperm RNA content using microarrays in asthenozoospermic patients (low motility). We started the present project to with the goal to characterize the RNA expression in asthenozoospermic infertile patients as compared to normozoospermic fertile controls. We selected four normal fertile donors and four severe asthenozoospermic infertile patients. Equal amounts of RNA were extracted from the sperm samples, subjected to different quality controls and hybridized to the Affymetrix U133 Plus version 2 arrays.

2012-03-15 | E-GEOD-34514 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data