320 Analyses of inter-individual variations of sperm DNA methylation and their potential implications in cattle

Abstract Background: DNA methylation has been shown to be involved in many biological processes, including X chromosome inactivation in females, paternal genomic imprinting, and others. Results: Based on the correlation patterns of methylation levels of neighboring CpG sites among 28 sperm whole genome bisulfite sequencing (WGBS) data (486×coverage), we obtained 31,272 methylation haplotype blocks (MHBs). Among them, we defined conserved methylated regions (CMRs), variably methylated regions (VMRs) and highly variably methylated regions (HVMRs) among individuals, and showed that HVMRs might play roles in transcriptional regulation and function in complex traits variation and adaptive evolution by integrating evidence from traditional and molecular quantitative trait loci (QTL), and selection signatures. Using a weighted correlation network analysis (WGCNA), we also detected a co-regulated module of HVMRs that was significantly associated with reproduction traits, and enriched for glycosyltransferase genes, which play critical roles in spermatogenesis and fertilization. Additionally, we identified 46 VMRs significantly associated with reproduction traits, nine of which were regulated by cis-SNPs, implying the possible intrinsic relationships among genomic variations, DNA methylation, and phenotypes. These significant VMRs were co-localized (± 10kb) with genes related to sperm motility and reproduction, including ZFP36L1, CRISP2 and HGF. We provided further evidence that rs109326022 within a predominant QTL on BTA18 might influence the reproduction traits through regulating the methylation level of nearby genes JOSD2 and ASPDH in sperm. Conclusion: In summary, our results demonstrated associations of sperm DNA methylation with reproduction traits, highlighting the potential of epigenomic information in genomic improvement programs for cattle.

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Analyses of inter-individual variations of sperm DNA methylation and their potential implications in cattle

BMC Genomics ◽

10.1186/s12864-019-6228-6 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 3

Author(s):

Shuli Liu ◽

Lingzhao Fang ◽

Yang Zhou ◽

Daniel J.A. Santos ◽

Ruidong Xiang ◽

...

Keyword(s):

Dna Methylation ◽

Complex Traits ◽

Sperm Dna ◽

Individual Variations ◽

Reproduction Traits ◽

Genome Bisulfite Sequencing ◽

Improvement Programs ◽

And Function ◽

Weighted Correlation ◽

Sperm Dna Methylation

Abstract Background DNA methylation has been shown to be involved in many biological processes, including X chromosome inactivation in females, paternal genomic imprinting, and others. Results Based on the correlation patterns of methylation levels of neighboring CpG sites among 28 sperm whole genome bisulfite sequencing (WGBS) data (486 × coverage), we obtained 31,272 methylation haplotype blocks (MHBs). Among them, we defined conserved methylated regions (CMRs), variably methylated regions (VMRs) and highly variably methylated regions (HVMRs) among individuals, and showed that HVMRs might play roles in transcriptional regulation and function in complex traits variation and adaptive evolution by integrating evidence from traditional and molecular quantitative trait loci (QTL), and selection signatures. Using a weighted correlation network analysis (WGCNA), we also detected a co-regulated module of HVMRs that was significantly associated with reproduction traits, and enriched for glycosyltransferase genes, which play critical roles in spermatogenesis and fertilization. Additionally, we identified 46 VMRs significantly associated with reproduction traits, nine of which were regulated by cis-SNPs, implying the possible intrinsic relationships among genomic variations, DNA methylation, and phenotypes. These significant VMRs were co-localized (± 10 kb) with genes related to sperm motility and reproduction, including ZFP36L1, CRISP2 and HGF. We provided further evidence that rs109326022 within a predominant QTL on BTA18 might influence the reproduction traits through regulating the methylation level of nearby genes JOSD2 and ASPDH in sperm. Conclusion In summary, our results demonstrated associations of sperm DNA methylation with reproduction traits, highlighting the potential of epigenomic information in genomic improvement programs for cattle.

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160 Studies of Sperm DNA Methylation Variations and Their Potential Regulations on Production and Reproduction Traits in Cattle and Pigs

Journal of Animal Science ◽

10.1093/jas/skab235.158 ◽

2021 ◽

Vol 99 (Supplement_3) ◽

pp. 88-89

Author(s):

Ying Yu ◽

Siqian Chen ◽

Shuli Liu ◽

Lingzhao Fang ◽

Shengli Zhang

Keyword(s):

Dna Methylation ◽

Production Traits ◽

Large White ◽

Pig Breeds ◽

Sperm Dna ◽

Differentially Methylated Genes ◽

Public Data ◽

Reproduction Traits ◽

Improvement Programs ◽

Sperm Dna Methylation

Abstract Identification of inter-individual variations of sperm DNA methylation is very essential for elucidating phenotypic variation of reproduction and production traits. We had generated 28 sperm whole genome sequencing (WGBS) data from healthy individuals. We detected 46 variably methylated regions (VMRs) significantly (P < 5.77 × 10−5) associated with reproduction traits. These significant VMRs were also co-localized (±10 kb) with genes related to sperm motility and reproduction, including ZFP36L1, CRISP2 and HGF. To further identify epigenomic markers associated with reproduction and production traits, we generated WGBS dada for a specific pair of monozygotic twin artificial insemination Holstein bulls with moderately different sperm qualities (Bull1 > Bull2). We found 528 differentially methylated regions between the twin bulls, which spanned or overlapped with 309 differentially methylated genes (DMG). These DMG were particularly associated with reproduction, embryo development and the nervous system. To further obtain DNA methylation markers involved in the diversity of porcine reproduction and production traits due to long-term artificial selection, we profiled sperm DNA methylation of three commercial pig breeds--Duroc, Landrace and Large White. we found the hypomethylated regions (HMRs) were highly conserved among pig breeds, while 1040–1666 breed-specific HMRs were identified and associated with the QTLs of embryonic developmental and phenotypic changes. By integrating reduced representation bisulfite sequencing public data of pig testis, we further defined 1743 conservative HMRs between sperm and testis, which may play a role in spermatogenesis process. Overall, our studies demonstrated associations of sperm DNA methylation with bovine and porcine production and reproduction traits, highlighting the potential of epigenomic information in genomic improvement programs for livestock. (*: [email protected])

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Integrating Signals from Sperm Methylome Analysis and Genome-Wide Association Study for a Better Understanding of Male Fertility in Cattle

Epigenomes ◽

10.3390/epigenomes3020010 ◽

2019 ◽

Vol 3 (2) ◽

pp. 10 ◽

Cited By ~ 5

Author(s):

Lingzhao Fang ◽

Yang Zhou ◽

Shuli Liu ◽

Jicai Jiang ◽

Derek M. Bickhart ◽

...

Keyword(s):

Dna Methylation ◽

Complex Traits ◽

Male Fertility ◽

Genome Wide Association ◽

Human Society ◽

Potential Candidate ◽

Genome Wide ◽

Sperm Dna ◽

Genomic Regions ◽

Sperm Dna Methylation

Decreased male fertility is a big concern in both human society and the livestock industry. Sperm DNA methylation is commonly believed to be associated with male fertility. However, due to the lack of accurate male fertility records (i.e., limited mating times), few studies have investigated the comprehensive impacts of sperm DNA methylation on male fertility in mammals. In this study, we generated 10 sperm DNA methylomes and performed a preliminary correlation analysis between signals from sperm DNA methylation and signals from large-scale (n = 27,214) genome-wide association studies (GWAS) of 35 complex traits (including 12 male fertility-related traits). We detected genomic regions, which experienced DNA methylation alterations in sperm and were associated with aging and extreme fertility phenotypes (e.g., sire-conception rate or SCR). In dynamic hypomethylated regions (HMRs) and partially methylated domains (PMDs), we found genes (e.g., HOX gene clusters and microRNAs) that were involved in the embryonic development. We demonstrated that genomic regions, which gained rather than lost methylations during aging, and in animals with low SCR were significantly and selectively enriched for GWAS signals of male fertility traits. Our study discovered 16 genes as the potential candidate markers for male fertility, including SAMD5 and PDE5A. Collectively, this initial effort supported a hypothesis that sperm DNA methylation may contribute to male fertility in cattle and revealed the usefulness of functional annotations in enhancing biological interpretation and genomic prediction for complex traits and diseases.

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Refraining from use diminishes cannabis-associated epigenetic changes in human sperm

Environmental Epigenetics ◽

10.1093/eep/dvab009 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Rose Schrott ◽

Susan K Murphy ◽

Jennifer L Modliszewski ◽

Dillon E King ◽

Bendu Hill ◽

...

Keyword(s):

Dna Methylation ◽

Early Development ◽

Bisulfite Sequencing ◽

Human Sperm ◽

Whole Genome ◽

Epigenetic Changes ◽

Cpg Sites ◽

Sperm Dna ◽

Genome Bisulfite Sequencing ◽

Sperm Dna Methylation

Abstract Cannabis use alters sperm DNA methylation, but the potential reversibility of these changes is unknown. Semen samples from cannabis users and non-user controls were collected at baseline and again following a 77-day period of cannabis abstinence (one spermatogenic cycle). Users and controls did not significantly differ by demographics or semen analyses. Whole-genome bisulfite sequencing identified 163 CpG sites with significantly different DNA methylation in sperm between groups (P < 2.94 × 10−9). Genes associated with altered CpG sites were enriched with those involved in development, including cardiogenesis and neurodevelopment. Many of the differences in sperm DNA methylation between groups were diminished after cannabis abstinence. These results indicate that sustained cannabis abstinence significantly reduces the number of sperm showing cannabis-associated alterations at genes important for early development.

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Early-Life Exposure to Environmental Contaminants Perturbs the Sperm Epigenome and Induces Negative Pregnancy Outcomes for Three Generations via the Paternal Lineage

Epigenomes ◽

10.3390/epigenomes5020010 ◽

2021 ◽

Vol 5 (2) ◽

pp. 10

Author(s):

Clotilde Maurice ◽

Mathieu Dalvai ◽

Romain Lambrot ◽

Astrid Deschênes ◽

Marie-Pier Scott-Boyer ◽

...

Keyword(s):

Dna Methylation ◽

Pregnancy Outcomes ◽

Sperm Quality ◽

The Arctic ◽

Congenital Defects ◽

Developmental Defects ◽

Early Life Exposure ◽

Sperm Dna ◽

Inuit Population ◽

Sperm Dna Methylation

Due to the grasshopper effect, the Arctic food chain in Canada is contaminated with persistent organic pollutants (POPs) of industrial origin, including polychlorinated biphenyls and organochlorine pesticides. Exposure to POPs may be a contributor to the greater incidence of poor fetal growth, placental abnormalities, stillbirths, congenital defects and shortened lifespan in the Inuit population compared to non-Aboriginal Canadians. Although maternal exposure to POPs is well established to harm pregnancy outcomes, paternal transmission of the effects of POPs is a possibility that has not been well investigated. We used a rat model to test the hypothesis that exposure to POPs during gestation and suckling leads to developmental defects that are transmitted to subsequent generations via the male lineage. Indeed, developmental exposure to an environmentally relevant Arctic POPs mixture impaired sperm quality and pregnancy outcomes across two subsequent, unexposed generations and altered sperm DNA methylation, some of which are also observed for two additional generations. Genes corresponding to the altered sperm methylome correspond to health problems encountered in the Inuit population. These findings demonstrate that the paternal methylome is sensitive to the environment and that some perturbations persist for at least two subsequent generations. In conclusion, although many factors influence health, paternal exposure to contaminants plays a heretofore-underappreciated role with sperm DNA methylation contributing to the molecular underpinnings involved.

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Sperm DNA methylation mediates the association of male age on reproductive outcomes among couples undergoing infertility treatment

Scientific Reports ◽

10.1038/s41598-020-80857-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Oladele A. Oluwayiose ◽

Haotian Wu ◽

Hachem Saddiki ◽

Brian W. Whitcomb ◽

Laura B. Balzer ◽

...

Keyword(s):

Dna Methylation ◽

Developed Countries ◽

Infertility Treatment ◽

Reproductive Outcomes ◽

Neurodevelopmental Outcomes ◽

Male Age ◽

Age Related ◽

Sperm Dna ◽

Increased Risk ◽

Sperm Dna Methylation

AbstractParental age at time of offspring conception is increasing in developed countries. Advanced male age is associated with decreased reproductive success and increased risk of adverse neurodevelopmental outcomes in offspring. Mechanisms for these male age effects remain unclear, but changes in sperm DNA methylation over time is one potential explanation. We assessed genome-wide methylation of sperm DNA from 47 semen samples collected from male participants of couples seeking infertility treatment. We report that higher male age was associated with lower likelihood of fertilization and live birth, and poor embryo development (p < 0.05). Furthermore, our multivariable linear models showed male age was associated with alterations in sperm methylation at 1698 CpGs and 1146 regions (q < 0.05), which were associated with > 750 genes enriched in embryonic development, behavior and neurodevelopment among others. High dimensional mediation analyses identified four genes (DEFB126, TPI1P3, PLCH2 and DLGAP2) with age-related sperm differential methylation that accounted for 64% (95% CI 0.42–0.86%; p < 0.05) of the effect of male age on lower fertilization rate. Our findings from this modest IVF population provide evidence for sperm methylation as a mechanism of age-induced poor reproductive outcomes and identifies possible candidate genes for mediating these effects.

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Impairment of sperm DNA methylation in male infertility: a meta-analytic study

Andrology ◽

10.1111/andr.12379 ◽

2017 ◽

Vol 5 (4) ◽

pp. 695-703 ◽

Cited By ~ 52

Author(s):

D. Santi ◽

S. De Vincentis ◽

E. Magnani ◽

G. Spaggiari

Keyword(s):

Dna Methylation ◽

Male Infertility ◽

Analytic Study ◽

Sperm Dna ◽

Sperm Dna Methylation

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Oxidative stress underlies heritable impacts of paternal cigarette smoke exposure

10.1101/750638 ◽

2019 ◽

Author(s):

Patrick J Murphy ◽

Jingtao Guo ◽

Timothy G Jenkins ◽

Emma R James ◽

John R Hoidal ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Dna Methylation ◽

Cigarette Smoke ◽

Cigarette Smoke Exposure ◽

Epigenetic Changes ◽

Sperm Dna ◽

Increased Risk ◽

Paternal Smoking ◽

Sperm Dna Methylation

SUMMARYPaternal cigarette smoke (CS) exposure is associated with increased risk of behavioral disorders and cancer in offspring, but the mechanism has not been identified. This study used mouse models to evaluate: 1) what impact paternal CS exposure has on sperm DNA methylation (DNAme), 2) whether sperm DNAme changes persist after CS exposure ends, 3) the degree to which DNAme and gene expression changes occur in offspring and 4) the mechanism underlying impacts of CS exposure. We demonstrate that CS exposure induces sperm DNAme changes that are partially corrected within 28 days of removal from CS exposure. Additionally, paternal smoking causes changes in neural DNAme and gene expression in offspring. Remarkably, the effects of CS exposure are largely recapitulated in oxidative stress-compromised Nrf2-/- mice and their offspring, independent of paternal smoking. These results demonstrate that paternal CS exposure impacts offspring phenotype and that oxidative stress underlies CS induced heritable epigenetic changes.

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