Impact of male fertility status on the transcriptome of the bovine epididymis

Légaré, Christine; Akintayo, Ayodele; Blondin, Patrick; Calvo, Ézéquiel; Sullivan, Robert

doi:10.1093/molehr/gax019

Cited by 47 publications

(28 citation statements)

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“…Male Tspan8 −/− mice are fertile and viable with no major abnormalities (Champy et al, 2011). As Sullivan, Belleannee, Jonge, & Barratt, 2017), the delivery of proteins responsible for sperm maturation may allude to problems of post-testicular maturation as a contributor to sperm dysfunction (Legare, Akintayo, Blondin, Calvo, & Sullivan, 2017).…”

Section: Discussionmentioning

confidence: 99%

Proteomic markers of low and high fertility bovine spermatozoa separated by Percoll gradient

D’Amours

Calvo

Bourassa

et al. 2019

Molecular Reproduction Devel

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In the context of artificial insemination, male fertility is defined as the ability to produce functional spermatozoa able to withstand cryopreservation. We hypothesized that interindividual variations in fertility depend on the proportion of the fully functional sperm population contained in the insemination dose. The objective of this study was to identify protein markers of the fully functional sperm subpopulation. Insemination doses from four high‐fertility (HF) and four low‐fertility (LF) bulls with comparable post‐thaw quality parameters were selected for proteomic analysis using iTRAQ technology. Thawed semen was centrifuged through a Percoll gradient to segregate the motile (high density [HD]) from the immotile (low density [LD]) sperm populations. Sperm proteins were extracted with sodium deoxycholate and four groups were compared: LD and HD spermatozoa from LF and HF bulls. A total of 498 unique proteins were identified and quantified. Comparison of HD spermatozoa from HF and LF bulls revealed that five proteins were significantly more abundant in the HF group (AK8, TPI1, TSPAN8, OAT, and DBIL5) whereas five proteins were more abundant in the LF group (RGS22, ATP5J, CLU, LOC616319, and CCT5). Comparison of LD spermatozoa from HF and LF bulls revealed that four proteins were significantly more abundant in the HF group (IL4I1, CYLC2, OAT, and ARMC3) whereas 15 proteins were significantly more abundant in the LF group (HADHA, HSP90AA1, DNASE1L3, SLC25A20, GPX5, TCP1, HIP1, CLU, G5E622, LOC616319, HSPA2, NUP155, DPY19L2, SPERT, and SERPINE2). DBIL5, TSPAN8, and TPI1 showed potential as putative markers of the fully functional sperm subpopulation.

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Section: Discussionmentioning

confidence: 99%

Proteomic markers of low and high fertility bovine spermatozoa separated by Percoll gradient

D’Amours

Calvo

Bourassa

et al. 2019

Molecular Reproduction Devel

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“…However, the marker density of previous association studies was low resulting in large QTL confidence intervals that contained many plausible candidate genes, thus precluding the identification of causal variants. The analysis of transcriptional profiles of testicular tissue from fertile and subfertile bulls revealed differentially expressed transcripts that are supposed to be relevant for testis development and spermatogenesis [34,35]. Using a candidate gene approach, a missense variant (rs136195618) in the PROP1 gene was postulated to be associated with bull fertility [36].…”

Section: Introductionmentioning

confidence: 99%

Activation of cryptic splicing in bovineWDR19is associated with reduced semen quality and male fertility

Hiltpold

Niu²,

Kadri

et al. 2020

Preprint

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Cattle are uniquely suited to investigate the genetics of male reproduction disorders, as semen quality and fertility are recorded for all ejaculates of artificial insemination bulls. Using 26,090 ejaculates of 794 Brown Swiss bulls, we analysed ejaculate volume, sperm concentration, sperm motility, sperm head and tail anomalies, and bull fertility. The heritability of the six semen traits was between 0 and 0.26. Genome-wide association testing between semen quality and 607,511 SNPs reveaed a QTL on bovine chromosome 6 that was associated with sperm motility (P = 2.5 x 10 -27 ), head (P = 2.0 x 10 -44 ) and tail anomalies (P = 7.2 x 10 -49 ) and insemination success (P = 9.9 x 10 -13 ). The QTL harbors a recessive allele that compromises semen quality and male fertility. We replicated the effect of the QTL on fertility (P = 7.1 x 10 -32 ) in 2481 bulls from an independent cohort of Brown Swiss bulls. The analysis of whole-genome sequencing data revealed that a synonymous variant (BTA6:58373887C>T, rs474302732) in WDR19 encoding WD repeat-containing protein 19 was in linkage disequilibrium with the fertility-associated haplotype. WD repeat-containing protein 19 is a constituent of the intraflagellar transport complex that is essential for the physiological function of motile cilia and flagella. Bioinformatic and transcription analyses showed that the BTA6:58373887 T-allele activates a cryptic splice site that eliminates three evolutionarily conserved amino acids from the WD-repeat domain, thus reducing semen quality and fertility. Western blot analysis demonstrated that the BTA6:58373887 T-allele decreases the WDR19 protein expression. We make the remarkable observation that, in spite of negative effects on semen quality and bull fertility, the deleterious allele has a frequency of 24 % in the Brown Swiss population. Our findings are the first to uncover a variant that controls quantitative variation in semen quality and male fertility in cattle. Author summaryMale reproductive disorders occur in many species. In cattle farming, artificial insemination is widely used. To ensure high fertilization rates, the quality of each ejaculate is recorded and the insemination success is monitored for every artificial insemination bull. We analyse semen quality and microarray-called genotypes at more than 600,000 genome-wide SNP markers in 794 bulls to identify a recessive allele that compromises semen quality and fertility. We take advantage of whole-genome sequencing to pinpoint a variant in the coding sequence of WDR19 encoding WD repeat-containing protein 19 that activates a novel exonic splice site. Our results indicate that cryptic splicing in WDR19 is associated with reduced male reproductive performance in cattle. This is the first report to reveal a variant associated with quantitative variation in bovine semen quality.

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“…Furthermore, another important group of genes, Lipocalins such as LCN9 (lipocalin 9), LCN6 (lipocalin 6), LCN12 (lipocalin 12) [49], which are all downregulated in the epididymis of infertile male cattleyak as compared to yak, consist of a family of proteins that play a role in the transportation of hydrophobic ligands, for instance, fatty acids retinoids and steroids to both the epithelium lining of the epididymis and the spermatozoa. LCN9 (-12.80 log2-fold change) which is reported to function in the transportation of luminal hydrophobic protein ligands to specific cells of epithelium lining of the epididymis [31] has an important but non-redundant function in male fertility. The functions of all the other epididymal Lipocalins, however, have not been so far well understood [50].…”

Section: Discussionmentioning

confidence: 99%

“…SERPINA1 (serpin family A member 1), lack of protein C inhibitor Serpina5 were found to cause infertility [56] while LOC523530 (nuclear RNA export factor 3), an epididymis-specific expression in principle cells regulates the expression of TGF-β3 in an mRNA export activity [57]. FABP4 (fatty acid-binding protein 4) associated with the stabilization of the sperm flagellum [58], CCR5 (C-C chemokine receptor type 5) essential for sperm motility, hyper-activation and acrosome reaction [18], GRIA2 (glutamate ionotropic receptor AMPA type subunit 2) functions in ion channels [31] and ENTPD3 (Ectonucleoside triphosphate) participates in smooth muscle contraction, steroidogenesis and spermatogenesis, and also regulates trans epithelial transport [59].…”

Section: Discussionmentioning

confidence: 99%

“…Among the top 30 DEGs, majority belonged to ß -defensins members of gene family i.e DEFB129 (defensin beta 129), DEFB124 (Defensin. beta 124), DEFB122A (beta-defensin 122a), DEFB122 (beta-defensin 122) and CST11(cystatin-11 precursor), CLEC4D (C-type lectin domain family 4 member D), LY6G5C (lymphocyte antigen 6 family member G5C), LY6G5B (lymphocyte antigen 6 family member G5B), CLEC4D (C-type lectin domain family 4 member D) and UBQLN2 (ubiquilin 2) were all associated with antimicrobial activity, anti-mycobacterial immunity, sperm protection, motility and auto-immune responses [30][31][32][33][34].…”

Section: Comparative Analysis Of Gene Expressionmentioning

confidence: 99%

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Comparative RNA-Seq Analysis of Differentially Expressed Genes in the Epididymides of Yak and Cattleyak

Zhao

Mengal

Yuan

et al. 2019

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Background: Cattleyak are the Fl hybrids between (♀) yak (Bos grunniens) and (♂) cattle (Bos taurus). Cattleyak exhibit higher capability in adaptability to a harsh environment and display much higher performances in production than the yak and cattle. The cattleyak, however, are females fertile but males sterile. All previous studies greatly focused on testes tissues to study the mechanism of male infertility in cattleyak. However, so far, no transcriptomic study has been conducted on the epididymides of yak and cattleyak. Objective: Our objective was to perform comparative transcriptome analysis between the epididymides of yak and cattleyak and predict the etiology of male infertility in cattleyak. Methods: We performed comparative transcriptome profiles analysis by mRNA sequencing in the epididymides of yak and cattleyak. Results: In total 3008 differentially expressed genes (DEGs) were identified in cattleyak, out of which 1645 DEGs were up-regulated and 1363 DEGs were down-regulated. Thirteen DEGs were validated by quantitative real-time PCR. DEGs included certain genes that were associated with spermatozoal maturation, motility, male fertility, water and ion channels, and beta-defensins. LCN9, SPINT4, CES5A, CD52, CST11, SERPINA1, CTSK, FABP4, CCR5, GRIA2, ENTPD3, LOC523530 and DEFB129, DEFB128, DEFB127, DEFB126, DEFB124, DEFB122A, DEFB122, DEFB119 were all downregulated, whereas NRIP1 and TMEM212 among top 30 DEGs were upregulated. Furthermore, protein processing in endoplasmic reticulum pathway was ranked at top-listed three significantly enriched KEGG pathways that as a consequence of abnormal expression of ER-associated genes in the entire ER protein processing pathway might have been disrupted in male cattleyak which resulted in the downregulation of several important genes. All the DEGs enriched in this pathway were downregulated except NEF. Conclusion: Taken together, our findings revealed that there were marked differences in the epididymal transcriptomic profiles of yak and cattleyak. The DEGs were involved in spermatozoal maturation, motility, male fertility, water and ion channels, and beta-defensins. Abnormal expression of ERassociated genes in the entire ER protein processing pathway may have disrupted protein processing pathway in male cattleyak resulting in the downregulation of several important genes involved in sperm maturation, motility and defense.

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Impact of male fertility status on the transcriptome of the bovine epididymis

Abstract: This work was supported by a grant to R.S. from the Natural Sciences and Engineering Research Council (NSERC) of Canada. C.L., A.A., E.C. and R.S. have no conflict of interest to declare. P.B. is R&D director at Alliance Boviteq Inc., a bovine artificial insemination company.

Cited by 47 publications

References 43 publications

Proteomic markers of low and high fertility bovine spermatozoa separated by Percoll gradient

Proteomic markers of low and high fertility bovine spermatozoa separated by Percoll gradient

Activation of cryptic splicing in bovineWDR19is associated with reduced semen quality and male fertility

Comparative RNA-Seq Analysis of Differentially Expressed Genes in the Epididymides of Yak and Cattleyak

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