B0367d29-351c-4579-96cb-818a690109d4 - samples
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PROVIDER: EGAD00001007085 | EGA |
REPOSITORIES: EGA
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Project description:Human TEX101 is a testis-specific cell membrane protein expressed exclusively in male germ cells and a validated biomarker of male infertility. TEX101 was suggested to function as a cell surface chaperone of numerous proteins involved in sperm migration and sperm-egg interaction. However, the precise functional roles of human TEX101 in spermatogenesis and fertilization are unknown. Here, we show that a common homozygous variant rs35033974 of TEX101 (G99V) with ~1% frequency in the general population may be associated with idiopathic male infertility. Spermatozoa from patients with homozygous rs35033974 exhibited near-complete degradation of variant G99V TEX101 protein and concomitant degradation of its interactome, as revealed by proteomic measurements. Substantially reduced levels of numerous testis-specific membrane proteins involved in sperm migration and sperm-oocyte fusion (including LY6K, IZUMO3 and ADAM29) were confirmed in spermatozoa of men with homozygous G99V variant. These men were previously diagnosed with idiopathic male infertility or oligospermia and failed the treatment by intrauterine insemination. Collectively, these data may facilitate diagnostics of idiopathic male infertility, provides a rational for selection of male infertility treatments and validate TEX101 and its interactome as targets to develop non-hormonal male contraceptives.
2024-11-02 | MSV000096278 | MassIVE
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
Project description:We examine how NGS sequencing of sperm can provide a window as to how particular perturbations of the sperm RNA profile from baseline may be indicative of male factor infertility, and may thus provide direction as to proper course of infertility treatment for couple. NGS RNA-seq of 72 sperm samples from male partner of couples undergoing fertility treatment
2015-07-09 | E-GEOD-65683 | biostudies-arrayexpress
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
Project description:Human TEX101 is a testis-specific cell membrane protein expressed exclusively in male germ cells and a validated biomarker of male infertility. TEX101 was suggested to function as a cell surface chaperone of numerous proteins involved in sperm migration and sperm-egg interaction. However, the precise functional roles of human TEX101 in spermatogenesis and fertilization are unknown. Here, we show that a common homozygous variant rs35033974 of TEX101 (G99V) with ~1% frequency in the general population may be associated with idiopathic male infertility. Spermatozoa from patients with homozygous rs35033974 exhibited near-complete degradation of variant G99V TEX101 protein and concomitant degradation of its interactome, as revealed by proteomic measurements. Substantially reduced levels of numerous testis-specific membrane proteins involved in sperm migration and sperm-oocyte fusion (including LY6K, IZUMO3 and ADAM29) were confirmed in spermatozoa of men with homozygous G99V variant. These men were previously diagnosed with idiopathic male infertility or oligospermia and failed the treatment by intrauterine insemination. Collectively, these data may facilitate diagnostics of idiopathic male infertility, provides a rational for selection of male infertility treatments and validate TEX101 and its interactome as targets to develop non-hormonal male contraceptives.
2018-11-21 | PXD008333 | Pride
Project description:Environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of adult onset disease, including testis disease and male infertility. The exposure of a gestating female during the period of gonadal sex determination has been shown to promote sperm epimutations, differential DNA methylation regions (DMR), that transmit transgenerational disease to subsequent generations. The current study was designed to determine the impact of an altered sperm epigenome on the subsequent development of an adult somatic cell (Sertoli cell) that influences the onset of a specific disease (male infertility). A gestating female rat (F0 generation) was exposed to the agriculture fungicide vinclozolin during gonadal sex determination and then the subsequent F3 generation progeny used for the isolation of Sertoli cells and assessment of testis disease. As previously observed, a spermatogenic cell apoptosis was observed. The Sertoli cells that provide the physical and nutritional support for the spermatogenic cells were isolated and alterations in gene expression examined. Over 400 genes were differentially expressed in the F3 generation control versus vinclozolin lineage Sertoli cells. A number of specific signaling pathways and cellular processes were identified to be transgenerationally altered. One of the key metabolic processes affected was pyruvate/lactate production that is directly linked to spermatogenic cell viability. The Sertoli cell epigenome was also altered with over 100 promoter differential DNA methylation regions (DMR) modified in the vinclozolin F3 generation Sertoli cell. The genomic features and overlap with the sperm DMR were investigated. Observations demonstrate that the transgenerational sperm epigenetic alterations subsequently alters the development of a specific somatic cell (Sertoli cell) epigenome and transcriptome that then has a role in the adult onset disease (male infertility). The environmentally induced epigenetic transgenerational inheritance of testis disease appears to be a component of the molecular etiology of male infertility. Environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of adult onset male infertility. The exposure of a gestating female during the period of gonadal sex determination has been shown to promote sperm epimutations, differential DNA methylation regions (DMR), that transmit transgenerational disease to subsequent generations. The current study was designed to determine the impact of an altered sperm epigenome on the subsequent development of an adult somatic cell (Sertoli cell) that influences the onset of a specific disease (male infertility). A gestating female rat (F0 generation) was exposed to the agriculture fungicide vinclozolin during gonadal sex determination and then the subsequent F3 generation progeny used for the isolation of Sertoli cells and assessment of testis disease. The Sertoli cells provide the physical and nutritional support for the spermatogenic cells in the testis. The F3 generation Sertoli cells have an altered transcriptome and epigenome associated with adult onset testis disease. The environmentally induced epigenetic transgenerational inheritance of Sertoli cell abnormalities appears to be a component of the molecular etiology of male infertility. RNA samples from Sertoli cell of 3 F3-control lineage groups are compared to Sertoli cell of 3 F3-vinclozolin lineage groups
2012-09-27 | E-GEOD-41173 | biostudies-arrayexpress
Project description:Male infertility is widespread and estimated to affect 1 in 20 men. Whilst in some cases the aetiology of the condition is well understood, for at least 50% of men, the underlying cause is yet to be classified. The majority of infertile men produce enough spermatozoa, however it is a combination of poor sperm motility, associated with a modified cell morphology that contribute to infertility. One of the major limitations of using morphology to inform male fertility status is that the evaluation is highly subjective, due to the fact that it has to be done by microscopic examination. As such, biomarkers of male infertility are needed to help establish a more consistent diagnosis. In the present study, we compared nuclear extracts from both high- and low-quality spermatozoa by LC-MS/MS based proteomic analysis. Our data shows that nuclear retention of proteins is a common facet amongst low quality male reproductive cells. In particular, we demonstrate that the presence of Topoisomerase 2A in sperm heads, is highly correlated to poor head morphology. Topoisomerase A is therefore a potential new biomarker for confirming male infertility in clinical practice.
2019-06-10 | MSV000083954 | MassIVE
Project description:We examine how NGS sequencing of sperm can provide a window as to how particular perturbations of the sperm RNA profile from baseline may be indicative of male factor infertility, and may thus provide direction as to proper course of infertility treatment for couple.
2015-07-09 | GSE65683 | GEO
Project description:Infertility is a widespread problem, affecting around 15% of couples worldwide, and is defined as the inability to achieve pregnancy within one year despite unprotected intercourse 1. Infertility can be caused by either male or female reproductive issues. Various medical conditions including malignancies, infections, urogenital conditions, or genetic causes can contribute to male infertility. However, 30-40% of men in their reproductive age are affected by idiopathic infertility, according to the guidelines of European Association of Urology (EAU) 1. Towards a better understanding of male infertility, it is mandatory to achieve a comprehensive understanding of involved genes, their RNA transcripts, and regulatory factors, including miRNAs, which influence the expression level of proteins. Therefore, such proteins need to be identified to investigate their role in spermatogenesis and male infertility. Although there are numerous studies on RNAs, including miRNAs related to male infertility 2-9, there are few studies aiming to cover the whole proteome of human sperm 10. The sperm transcriptome comprises a total of 60,505 transcripts including 11,688 differentially expressed transcripts in infertile and fertile men, as reported by Joshi et al. (2022)11. The entire sperm proteome encompasses 6871 proteins, as summarized by Castillo et al. (2018)10. Nevertheless, there is still a lack of high-throughput studies aiming to identify dysregulated proteins in sperm from subfertile men. Only few studies focused on comparisons of the sperm proteome in men with asthenozoospermia and there is virtually no proteomic studies of oligoasthenozoospermic men 12. Some identified proteins in sperm have functions in maintaining sperm motility and enabling fertilization and are involved in structural composition and/or energy metabolism 12-14 and others are not yet functionally characterized. In this study, we employed Mass spectrometry (MS) technology that is still rarely used in the field of human reproductive research to investigate the proteomic landscape of human sperm and their differential expression patterns in men with subfertility.
2023-05-10 | PXD039703 | Pride
Project description:The aim of this study was to achieve a higher resolution of the human sperm proteome for better understanding of the molecular causes of male infertility. For this purpose, we examined the proteomic profiles of sperm from 76 men for proteins with deregulated abundances. Infertile men had abnormal semen parameters and were involuntarily childless. Men in the cohort with normal fertility had normozoospermia and had fathered children without medical assistance. Mass spectrometry analysis led to an in-depth reconstruction of the human sperm proteome. The corresponding genes were mainly involved in cellular motility, response to stimuli, adhesion, and reproduction. We also observed increasing numbers of at least three-fold differentially abundant sperm proteins from oligozoospermia and oligoasthenozoospermia to oligoasthenoteratozoospermia, compared with normozoospermia. Primarily, flagellar assembly and sperm motility, sperm-egg interaction, and male gametogenesis were affected. This suggests that sperm of infertile men carry signatures of impaired sperm production and are functionally impaired. Not least, we present new male infertility markers in addition to established ones.
2023-04-11 | PXD037531 | Pride