Dataset Information

Activation of cryptic splicing in bovine WDR19 is associated with reduced semen quality and male fertility.

ABSTRACT: Cattle are ideally suited to investigate the genetics of male reproduction, because semen quality and fertility are recorded for all ejaculates of artificial insemination bulls. We analysed 26,090 ejaculates of 794 Brown Swiss bulls to assess ejaculate volume, sperm concentration, sperm motility, sperm head and tail anomalies and insemination success. The heritability of the six semen traits was between 0 and 0.26. Genome-wide association testing on 607,511 SNPs revealed 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 an independent cohort of 2481 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 revealed that the BTA6:58373887 T-allele activates a cryptic exonic splice site that eliminates three evolutionarily conserved amino acids from WDR19. Western blot analysis demonstrated that the BTA6:58373887 T-allele decreases protein expression. We make the remarkable observation that, in spite of negative effects on semen quality and bull fertility, the BTA6:58373887 T-allele has a frequency of 24% in the Brown Swiss population. Our findings are the first to uncover a variant that is associated with quantitative variation in semen quality and male fertility in cattle.

SUBMITTER: Hiltpold M

PROVIDER: S-EPMC7252675 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Activation of cryptic splicing in bovine WDR19 is associated with reduced semen quality and male fertility.

Hiltpold Maya M Niu Guanglin G Kadri Naveen Kumar NK Crysnanto Danang D Fang Zih-Hua ZH Spengeler Mirjam M Schmitz-Hsu Fritz F Fuerst Christian C Schwarzenbacher Hermann H Seefried Franz R FR Seehusen Frauke F Witschi Ulrich U Schnieke Angelika A Fries Ruedi R Bollwein Heinrich H Flisikowski Krzysztof K Pausch Hubert H

PLoS genetics 20200514 5

Cattle are ideally suited to investigate the genetics of male reproduction, because semen quality and fertility are recorded for all ejaculates of artificial insemination bulls. We analysed 26,090 ejaculates of 794 Brown Swiss bulls to assess ejaculate volume, sperm concentration, sperm motility, sperm head and tail anomalies and insemination success. The heritability of the six semen traits was between 0 and 0.26. Genome-wide association testing on 607,511 SNPs revealed a QTL on bovine chromoso ...[more]

PMID: 32407316

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Project description:Study questionWhat are the relations among birthweight (BW), semen parameters and birth outcomes in a population-based sample?Summary answerBW is unrelated to semen parameters, which are in turn unrelated to birth outcomes.What is known alreadyIn clinical settings, there has been suggestion that semen parameters are related to BW when comparing fertile and infertile men; however, findings have been less clear in more general populations.Study design, size, durationQuestionnaire data and semen samples were collected at baseline from 427 male participants of the population-based Longitudinal Investigation of Fertility and the Environment (LIFE) prospective cohort study from 2005 to 2009, who were followed prospectively to assess pregnancy outcomes among 226 singleton births.Participants/materials, setting, methodsMen of at least 18 years of age who were married or in a committed relationship and trying to conceive were eligible for participation; physician-diagnosed infertility was an exclusion criterion. Participants were recruited from two geographic areas and semen samples were analyzed for 34 quality parameters categorized as general, motility, morphology, sperm head and sperm chromatin structure using methods including computer-aided semen analysis integrated visual optical system and sperm chromatin structure assay. Linear and mixed models were used for statistical analysis of the relations between men's BW, semen parameters, and BW, gestational age at delivery, birth length, head circumference and ponderal index of singleton births.Main results and the role of chanceNo association was observed between male BW and semen parameters or birth outcomes. Few associations were observed between semen parameters and birth outcomes, and the observed statistically significant associations were isolated and without a consistent pattern that would suggest an association between BW and birth outcomes.Limitations, reasons for cautionMen's BW was self-reported and may be subject to some imprecision. Semen analysis was performed the day after collection, an approach that impacts the assessment of motility and that may limit inference from our analyses of motility measures. In addition, inclusion criteria for selection into the cohort limits generalizability to generally healthy couples trying to conceive and without known subfertility.Wider implications of the findingsDespite suggestions from prior studies of male in utero exposures impacting BW and male reproductive health, there appears to be little support for such relations in this generally healthy population.Study funding/competing interest(s)Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (N01-HD-3-3355, N01-HD-3-3356 and NOH-HD-3-3358). The authors report no competing interests, and a Memo of Understanding with the National Institute of Occupational Safety and Health (NIOSH) for semen analysis.Trial registration numberNot applicable.

Project description:BackgroundTriclosan, a widely-used antimicrobial in personal care products, has shown endocrine disrupting activity in experimental studies. However, there is limited evidence from epidemiologic studies on health effects.ObjectiveTo examine the association between urinary triclosan concentrations and semen quality.MethodsA total of 262 men enrolled in the Environmental and Reproductive Health (EARTH) Study provided 581 paired urine and semen samples (2009-2017). Urinary triclosan concentrations were quantified and semen analysis was evaluated according to WHO guidelines. We used linear mixed regression models to estimate the associations between specific gravity-adjusted urinary triclosan concentrations with semen parameters, with a random intercept to account for multiple samples per man and adjusting for age, body mass index (BMI), smoking, physical activity, sexual abstinence time, and season and year of samples' collection.ResultsMen had a mean (standard deviation) age of 36.6 (5.24) years and BMI of 27.9 (5.94) kg/m2. Seventy four percent of the samples had detectable (>2.3 μg/L) concentrations. We did not observe significant dose response trends between SG-adjusted urinary triclosan concentrations and semen parameters. However, in the adjusted analysis, compared to men with non-detectable triclosan concentrations in the lowest quartile, those in the second, third, and fourth quartiles had -1.32% (95%CI: -2.04, -0.59), -0.91% (95%CI: -1.63, -0.18), and -0.46% (95%CI: -1.25, 0.33) lower percent morphologically normal sperm, respectively. Similarly, a lower percentage of morphologically normal sperm was found among men with detectable triclosan concentrations, compared to men with non-detectable triclosan [-0.96% (95% CI: -1.57, -0.35)]. In sensitivity analyses, there was stronger negative associations on the percent morphologically normal sperm in the earlier time period due to the significant negative trend in detectable triclosan concentrations over time.ConclusionDespite the lack of observed dose response relationship, we found consistent patterns of lower percent morphologically normal sperm for men with urinary triclosan in the 2nd or 3rd quartile compared to undetectable concentrations.This association was stronger for samples obtained prior to 2013 when triclosan was more often detectable in urine.

Dataset Information

Activation of cryptic splicing in bovine WDR19 is associated with reduced semen quality and male fertility.

Publications

Activation of cryptic splicing in bovine WDR19 is associated with reduced semen quality and male fertility.

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