A novel acrosomal protein, <scp>IQCF</scp>1, involved in sperm capacitation and the acrosome reaction

Peng, Fang; Xu, Wangjie; Li, D.; Zhao, Xiang; Dai, Jingbo; Wang, Zhong Min; Yan, Xiu-Juan; Qin, Mu; Zhang, Y.; Xu, Chen; Wang, L.; Qiao, Zhongdong

doi:10.1111/andr.296

Cited by 27 publications

(17 citation statements)

References 44 publications

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“…Luangpraseuth-Prosper et al [66] demonstrated that Topaz1-knockout mice presented meiotic arrest and male infertility. As for IQCF1, Fang et al [67] reported that this gene localizes in the acrosome and that it is involved in sperm capacitation in mice. Iqcf1 −/− mice were significantly less fertile than wild type mice [67].…”

Section: Gwas Analysismentioning

confidence: 99%

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A systems biology framework integrating GWAS and RNA-seq to shed light on the molecular basis of sperm quality in swine

et al. 2020

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Background Genetic pressure in animal breeding is sparking the interest of breeders for selecting elite boars with higher sperm quality to optimize ejaculate doses and fertility rates. However, the molecular basis of sperm quality is not yet fully understood. Our aim was to identify candidate genes, pathways and DNA variants associated to sperm quality in swine by analysing 25 sperm-related phenotypes and integrating genome-wide association studies (GWAS) and RNA-seq under a systems biology framework. Results By GWAS, we identified 12 quantitative trait loci (QTL) associated to the percentage of head and neck abnormalities, abnormal acrosomes and motile spermatozoa. Candidate genes included CHD2, KATNAL2, SLC14A2 and ABCA1. By RNA-seq, we identified a wide repertoire of mRNAs (e.g. PRM1, OAZ3, DNAJB8, TPPP2 and TNP1) and miRNAs (e.g. ssc-miR-30d, ssc-miR-34c, ssc-miR-30c-5p, ssc-miR-191, members of the let-7 family and ssc-miR-425-5p) with functions related to sperm biology. We detected 6128 significant correlations (P-value ≤ 0.05) between sperm traits and mRNA abundances. By expression (e)GWAS, we identified three trans-expression QTL involving the genes IQCJ, ACTR2 and HARS. Using the GWAS and RNA-seq data, we built a gene interaction network. We considered that the genes and interactions that were present in both the GWAS and RNA-seq networks had a higher probability of being actually involved in sperm quality and used them to build a robust gene interaction network. In addition, in the final network we included genes with RNA abundances correlated with more than four semen traits and miRNAs interacting with the genes on the network. The final network was enriched for genes involved in gamete generation and development, meiotic cell cycle, DNA repair or embryo implantation. Finally, we designed a panel of 73 SNPs based on the GWAS, eGWAS and final network data, that explains between 5% (for sperm cell concentration) and 36% (for percentage of neck abnormalities) of the phenotypic variance of the sperm traits. Conclusions By applying a systems biology approach, we identified genes that potentially affect sperm quality and constructed a SNP panel that explains a substantial part of the phenotypic variance for semen quality in our study and that should be tested in other swine populations to evaluate its relevance for the pig breeding sector.

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Section: Gwas Analysismentioning

confidence: 99%

“…As for IQCF1, Fang et al [67] reported that this gene localizes in the acrosome and that it is involved in sperm capacitation in mice. Iqcf1 −/− mice were significantly less fertile than wild type mice [67]. The QTL region on SSC13 I2 included the candidate protein kinase C delta (PRKCD) gene.…”

Section: Gwas Analysismentioning

confidence: 99%

A systems biology framework integrating GWAS and RNA-seq to shed light on the molecular basis of sperm quality in swine

et al. 2020

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“…The acrosome is a specialized organelle containing many hydrolytic enzymes that help sperm penetrates the zona pellucida of oocytes. [28][29][30] Several genes have been reported to be involved in acrosome formation in mice, including SPACA1, GOPC, PICK1, and so on. [20][21][22] In our studies, we found the expression levels of SPACA1 and PICK1 were significantly downregulated in Ccdc136 À/À mouse testes than Ccdc136 þ/À , which strongly suggested that deficiency of Ccdc136 leads to malformation of acrosome during spermatogenesis.…”

Section: Discussionmentioning

confidence: 99%

A Novel Testis-Specific Gene, Ccdc136, Is Required for Acrosome Formation and Fertilization in Mice

Qian

Ouyang

et al. 2016

Reprod. Sci.

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Testis-specific genes are essential for the spermatogenesis in mammalian male reproduction. In this study, we have identified a novel testis-specific gene, Ccdc136 (coiled-coil domain containing 136), from the results of high-throughput gene expression profiling in the developmental stage of mouse testes. Ccdc136 was conserved across species in evolution. Quantitative real-time polymerase chain reaction and Western blot analyses showed that Ccdc136 messenger RNA and protein were extraordinarily expressed in mouse testes, which was first presented at postnatal 3 week and increased in an age-dependent manner before adulthood. Immunofluorescence staining revealed that CCDC136 protein was most abundantly located in the acrosome of round spermatids and elongating spermatids within seminiferous tubules of the adult mouse testes. To investigate the function of Ccdc136 in mouse testes, we generated the Ccdc136-knockout mice using Cas9/RNA-mediated gene targeting technology. Interestingly, we found Ccdc136(-/-) males were infertile, due to severe defect of disrupting acrosome formation. The expression levels of proteins (SPACA1 and PICK1) involved in acrosome formation were significantly downregulated in the testes of Ccdc136(-/-) mice than wide-type mice. Moreover, in vitro fertilization assay revealed that anti-CCDC136 antibody could remarkably inhibit fertilization, suggesting CCDC136 also plays an important role in fertilization. All of these demonstrated the essential role of CCDC136-mediated acrosome formation in spermatogenesis and fertilization, which might also provide new insight into the genetic causes of human infertility.

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“…We detected several significant regions for HABN ( (Fang et al, 2015) reported that this gene localizes in the acrosome and that it is involved in sperm capacitation in mice. Iqcf1-/-mice were significantly less fertile than wild type mice (Fang et al, 2015). The QTL region on SSC13 I2 included the candidate Protein Kinase C Delta (PRKCD) gene.…”

Section: Gwas Analysismentioning

confidence: 93%

An integrative systems biology approach to identify the molecular basis of sperm quality in swine

Gòdia

Reverter

González-Prendes

et al. 2020

Preprint

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Background:Genetic pressure in animal breeding is sparking the interest to select for elite boars with higher sperm quality to maximize ejaculate doses and fertility rates. However, the molecular basis of sperm quality remains largely unexplored. In this study, we sought to identify candidate genes, pathways and DNA variants associated to sperm quality in swine by analyzing 25 sperm-related phenotypes using a systems biology approach that integrates GWAS and RNA-seq.Results:By GWAS, we identified 12 QTL regions associated to the percentage of head and neck abnormalities, abnormal acrosomes and motile spermatozoa. Candidate genes included CHD2, KATNAL2, SLC14A2 or ABCA1. By RNA-seq, we detected 6,128 significant correlations between sperm traits and gene RNA abundances. We built a gene interaction network with the GWAS and the RNA-seq data. To build a robust gene interaction network, only the pair-wise interactions present in both the genetic co-association and the RNA co-abundance network were kept. Moreover, we also included to the Final Network both the genes which RNA abundances correlated with more than 4 semen traits as well as the miRNAs interacting with the genes on the network. The Final Network was enriched for genes involved in gamete generation and development, meiotic cell cycle, DNA repair or embryo implantation. We finally designed a panel of 73 SNPs provided from the GWAS, eGWAS and the Final Network, that explains between 5 to 36% of the phenotypic variance of the sperm traits.Conclusions:By means of a systems biology approach, we identified potential key genes affecting sperm quality. Furthermore, we propose a SNP panel that might explain a substantial part of the genetic variance for semen quality in swine and may thus be of interest for the pig breeding sector.

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A novel acrosomal protein, IQCF1, involved in sperm capacitation and the acrosome reaction

Cited by 27 publications

References 44 publications

A systems biology framework integrating GWAS and RNA-seq to shed light on the molecular basis of sperm quality in swine

A systems biology framework integrating GWAS and RNA-seq to shed light on the molecular basis of sperm quality in swine

A Novel Testis-Specific Gene, Ccdc136, Is Required for Acrosome Formation and Fertilization in Mice

An integrative systems biology approach to identify the molecular basis of sperm quality in swine

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