A sperm-specific proteome-scale metabolic network model identifies non-glycolytic genes for energy deficiency in asthenozoospermia

Asghari, Arvand; Marashi, Sayed-Amir; Ansari-Pour, Naser

doi:10.1080/19396368.2016.1263367

Cited by 31 publications

(21 citation statements)

References 94 publications

(141 reference statements)

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“…The axonemal dyneins generate force through the hydrolysis of the ATP created in the mitochondria and bind to the structural components of the mictubules, such as tektins, to actively participate in flagellar movement 25 . In line with this fact, the expression of FH and TEKT1 is lower in semen samples with poor sperm motility (asthenozoospermia) 26 , indicating that SPANX-A/D family, through the interaction with both proteins FH and TEKT1, could be essential in human spermatozoa to meet energy demands for motility.…”

Section: Discussionmentioning

confidence: 73%

SPANX-A/D protein subfamily plays a key role in nuclear organisation, metabolism and flagellar motility of human spermatozoa

Urizar-Arenaza

Osinalde

Akimov

et al. 2020

Sci Rep

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Human sperm protein associated with the nucleus on the X chromosome (SpAnX) genes encode a protein family (SpAnX-A,-B,-c and-D), whose expression is limited to the testis and spermatozoa in normal tissues and to a wide variety of tumour cells. present only in hominids, SpAnX-A/D is exclusively expressed in post-meiotic spermatids and mature spermatozoa. However, the biological role of the protein family in human spermatozoa is largely unknown. combining proteomics and molecular approaches, the present work describes the presence of all isoforms of SpAnX-A/D in human spermatozoa and novel phosphorylation sites of this protein family. In addition, we identify 307 potential SpAnX-A/D interactors related to nuclear envelop, chromatin organisation, metabolism and cilia movement. Specifically, SPANX-A/D interacts with fumarate hydratase and colocalises with both fumarate hydratase and Tektin 1 proteins, involved in meeting energy demands for sperm motility, and with nuclear pore complex nucleoporins. We provide insights into the molecular features of sperm physiology describing for the first time a multifunctional role of SPANX-A/D protein family in nuclear envelope, sperm movement and metabolism, considered key functions for human spermatozoa. SpAnX-A/D family members, therefore, might be promising targets for sperm fertility management. Currently, over 186 million people worldwide have infertility problems 1 , and male factors represent approximately 40-50% of clinical infertility cases 2. Among other factors, anatomical or genetic abnormalities, problems in spermatogenesis or environmental factors 3 , are responsible for abnormal sperm parameters which contribute to male infertility. However, approximately 20-30% of men with normal sperm parameters have impaired fertility suggesting that male infertility can be caused by different deficiencies not yet described. The sperm protein associated with the nucleus mapped to the X chromosome (SPANX) family is a testis-specific multigene family. SPANX genes encode proteins that belong to the so-called "cancer testis antigens" (CTA) family, a group of proteins whose expression is limited to the testis and spermatozoa in normal tissues and to a wide variety of tumours 4,5. The SPANX family includes two subfamilies: the SPANX-N subfamily, composed of SPANX-N1,-N2,-N3,-N4 (in the locus Xq27.3) and-N5 (in the locus Xp11.22) that share a high level of sequence homology 6 ; and the SPANX-A/D subfamily, which includes SPANX-A1,-A2,-C,-D (in the locus Xq27.2) and-B (in the locus Xq27.1) with high sequence homology 5,7. Evolved from a common ancestor, the SPANX-N gene family is present in mice, rats and all primates, while the SPANX-A/D family is expressed only in hominids, including humans, bonobos and chimpanzees 8. All SPANX proteins exhibit a similar post-meiotic expression pattern during spermatogenesis, appearing for the first time in haploid spermatids 4,7,9. In mature spermatozoa, SPANX-N proteins are localised on the acrosome 6 , while SPANX-A/D proteins are expressed as dots

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Section: Discussionmentioning

confidence: 73%

SPANX-A/D protein subfamily plays a key role in nuclear organisation, metabolism and flagellar motility of human spermatozoa

Urizar-Arenaza

Osinalde

Akimov

et al. 2020

Sci Rep

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“…SLC25A20 encodes a carnitine carrier in the mitochondrial membrane that is involved in ATP production and cell energy metabolism and has been associated with human asthenozoospermia, aka low sperm motility (Asghari et al . ). Overall, our findings provide the foundation for future fine mapping and functional studies that seek to reveal the specific roles of this set of candidate genes in Jersey bull fertility.…”

Section: Discussionmentioning

confidence: 97%

Genetic dissection of bull fertility in US Jersey dairy cattle

2018

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SummaryThe service sire has been recognized as an important factor affecting herd fertility in dairy cattle. Recent studies suggest that genetic factors explain part of the difference in fertility among Holstein sires. The main objective of this study was to dissect the genetic architecture of sire fertility in US Jersey cattle. The dataset included 1.5 K Jersey bulls with sire conception rate (SCR) records and 96 K single nucleotide polymorphism (SNP) markers spanning the whole genome. The analysis included whole‐genome scans for both additive and non‐additive effects and subsequent functional enrichment analyses using KEGG Pathway, Gene Ontology (GO) and Medical Subject Headings (MeSH) databases. Ten genomic regions located on eight different chromosomes explained more than 0.5% of the additive genetic variance for SCR. These regions harbor genes, such as PKDREJ,EPB41L2,PDGFD,STX2,SLC25A20 and IP6K1, that are directly implicated in testis development and spermatogenesis, sperm motility and the acrosome reaction. In addition, the genomic scan for non‐additive effects identified two regions on BTA11 and BTA25 with marked recessive effects. These regions harbor three genes—FER1L5,CNNM4 and DNAH3—with known roles in sperm biology. Moreover, the gene‐set analysis revealed terms associated with calcium regulation and signaling, membrane fusion, sperm cell energy metabolism, GTPase activity and MAPK signaling. These gene sets are directly implicated in sperm physiology and male fertility. Overall, this integrative genomic study unravels genetic variants and pathways affecting Jersey bull fertility. These findings may contribute to the development of novel genomic strategies for improving sire fertility in Jersey cattle.

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“…The vacuolar ATPase ATP6V0A2 transcripts and proteins are down-regulated in the sperm of infertile men 27 . The pyrophosphatase www.nature.com/scientificreports www.nature.com/scientificreports/ PPA2 is located in the mitochondrial membrane and might be involved in the production of ATP, control of molecular processes linked to the launching of sperm capacitation and sperm motility 28 . PAIP2 is an inhibitor of translation and is linked to sperm maturation and male fertility 29 .…”

Section: Discussionmentioning

confidence: 99%

Identification of circular RNAs in porcine sperm and evaluation of their relation to sperm motility

Gòdia

Castelló

Rocco

et al. 2020

Sci Rep

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Circular RNAs (circRNAs) are emerging as a novel class of noncoding RNAs which potential role as gene regulators is quickly gaining interest. circRNAs have been studied in different tissues and cell types across several animal species. However, a thorough characterization of the circRNAome in ejaculated sperm remains unexplored. In this study, we profiled the sperm circRNA catalogue using 40 porcine ejaculates. A complex population of 1,598 circRNAs was shared in at least 30 of the 40 samples. Generally speaking, the predicted circRNAs presented low abundances and were tissue-specific. Around 80% of the circRNAs identified in the boar sperm were reported as novel. Results from abundance correlation between circRNAs and miRNAs together with the prediction of microRNA (miRNA) target sites in circRNAs suggested that circRNAs may act as miRNA sponges. Moreover, we found significant correlations between the abundance of 148 exonic circRNAs and sperm motility parameters. Two of these correlations, involving ssc_circ_1458 and ssc_circ_1321, were confirmed by RT-qPCR using 36 additional samples with extreme and opposite sperm motility values. Our study provides a thorough characterization of circRNAs in sperm and suggests that circRNAs hold potential as noninvasive biomarkers for sperm quality and male fertility.

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A sperm-specific proteome-scale metabolic network model identifies non-glycolytic genes for energy deficiency in asthenozoospermia

Cited by 31 publications

References 94 publications

SPANX-A/D protein subfamily plays a key role in nuclear organisation, metabolism and flagellar motility of human spermatozoa

SPANX-A/D protein subfamily plays a key role in nuclear organisation, metabolism and flagellar motility of human spermatozoa

Genetic dissection of bull fertility in US Jersey dairy cattle

Identification of circular RNAs in porcine sperm and evaluation of their relation to sperm motility

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