scholarly journals Oxidative stress underlies heritable impacts of paternal cigarette smoke exposure

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.

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

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.

scholarly journals Impact of acute exposure to cigarette smoke on airway gene expression

2018 ◽  
Vol 50 (9) ◽  
pp. 705-713 ◽  
Author(s):  
E. Billatos ◽  
A. Faiz ◽  
Y. Gesthalter ◽  
A. LeClerc ◽  
Y. O. Alekseyev ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Lung Cancer ◽  
Cigarette Smoke ◽  
Smoke Exposure ◽  
Acute Exposure ◽  
Cigarette Smoke Exposure ◽  
Airway Epithelial ◽  
Long Term Effects ◽  
Chronic Smoking

Background: Understanding effects of acute smoke exposure (ASE) on airway epithelial gene expression and their relationship with the effects of chronic smoke exposure may provide biological insights into the development of smoking-related respiratory diseases. Methods: Bronchial airway epithelial cell brushings were collected from 63 individuals without recent cigarette smoke exposure and before and 24 h after smoking three cigarettes. RNA from these samples was profiled on Affymetrix Human Gene 1.0 ST microarrays. Results: We identified 91 genes differentially expressed 24 h after ASE (false discovery rate < 0.25). ASE induced genes involved in xenobiotic metabolism, oxidative stress, and inflammation and repressed genes related to cilium morphogenesis and cell cycle. While many genes altered by ASE are altered similarly in chronic smokers, metallothionein genes are induced by ASE and suppressed in chronic smokers. Metallothioneins are also suppressed in current and former smokers with lung cancer relative to those without lung cancer. Conclusions: Acute exposure to as little as three cigarettes and chronic smoking induce largely concordant changes in airway epithelial gene expression. Differences in short-term and long-term effects of smoking on metallothionein expression and their relationship to lung cancer requires further study given these enzymes’ role in the oxidative stress response.

scholarly journals Age-related sperm DNA methylation changes are transmitted to offspring and associated with abnormal behavior and dysregulated gene expression

2014 ◽  
Vol 20 (8) ◽  
pp. 995-1001 ◽  
Author(s):  
M H Milekic ◽  
Y Xin ◽  
A O’Donnell ◽  
K K Kumar ◽  
M Bradley-Moore ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Abnormal Behavior ◽  
Age Related ◽  
Sperm Dna ◽  
Sperm Dna Methylation

scholarly journals Aging-induced Changes in Sperm DNA Methylation are Modified by Low Dose of Perinatal Flame retardants

2020 ◽  
Author(s):  
J.Richard Pilsner ◽  
Alex Shershebnev ◽  
Haotian Wu ◽  
Chelsea Marcho ◽  
Olga Dribnokhodova ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Flame Retardants ◽  
Natural Aging ◽  
Paternal Age ◽  
Epigenetic Changes ◽  
Age Related ◽  
Sperm Dna ◽  
Age Dependent ◽  
Environmental Xenobiotic ◽  
Sperm Dna Methylation

Advanced paternal age at fertilization has been suggested to be a risk factor for neurodevelopmental, psychiatric and other disorders in offspring. One emerging hypothesis suggests that altered offspring phenotype is linked with age-related accumulation of epigenetic changes in the sperm of fathers. Given that paternal age is increasing in the developed world, understanding aging-related epigenetic changes in sperm is needed as well as environmental factors that modify such changes. In this study, we characterize age-dependent changes in sperm DNA methylation profiles between young pubertal (postnatal day (PNDs) 65) and mature (PND120) Wistar rats. We also analyze these changes in rats exposed perinatally to 0.2 mg/kg of ubiquitous environmental xenobiotic 2,2&rsquo;,4,4&rsquo;-tetrabromodiphenyl ether (BDE-47). Reduced representation bisulfite sequencing (RRBS) libraries were prepared from caudal epididymal sperm DNA and differentially methylated regions (DMRs; &ge; 10x coverage depth, &ge; 3 CpGs per cluster, &ge; 5% methylation change, q &lt; 0.05) were identified via MethPipe package. In control animals, 5,319 age-dependent DMRs were identified, with 99.3% DMRs hypermethylated in mature animals compared to young pubertal rats. These age-related DMRs were enriched for functional categories essential for embryonic development, such as pattern specification, forebrain and sensory organ development, Hippo and Wnt pathways. Age-related changes in sncRNA, reported in different study, target similar list of genes and biological categories.In BDE-47 exposed rats, sperm DNA methylation was higher in young pubertal and lower in mature animals when compared to controls, which resulted in a significant attenuation in the number of age-dependent DMRs (N = 189) identified in the exposed group. In conclusion, our results indicate that the natural aging process has profound effects on sperm methylation levels and this effect may be modified by environmental exposures. Moreover, our results further support the role of epigenetic mechanisms as a likely link betwen paternal age and offspring health and development.

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

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 &lt; 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.

scholarly journals Neurological Effects in the Offspring After Switching From Tobacco Cigarettes to E-Cigarettes During Pregnancy in a Mouse Model

2019 ◽  
Vol 172 (1) ◽  
pp. 191-200 ◽  
Author(s):  
Tara Nguyen ◽  
Gerard E Li ◽  
Hui Chen ◽  
Charles G Cranfield ◽  
Kristine C McGrath ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cigarette Smoke ◽  
Neuronal Cell ◽  
Smoke Exposure ◽  
Neurological Deficits ◽  
Health Concern ◽  
Cigarette Smoke Exposure ◽  
Global Dna Methylation ◽  
Tobacco Cigarette

Abstract Maternal smoking is currently a public health concern and has been associated with a number of complications in the offspring. E-cigarettes are gaining popularity as a “safer” alternative to tobacco cigarettes during pregnancy, however, there are a limited number of studies to suggest that it is actually “safe.” Balb/C female mice were exposed to ambient air (n = 8; Sham), or tobacco cigarette smoke (n = 8; SE) before gestation, during gestation and lactation. A third group was exposed to cigarette smoke before gestation followed by e-cigarette aerosols during gestation and lactation (n = 8; Switch). Male offspring (12-week old, n = 10–14/group) underwent behavioral assessments to investigate short-term memory, anxiety, and activity using the novel object recognition and elevated plus maze tests. Brains were collected at postnatal day (P)1, P20, and Week 13 for global DNA methylation, epigenetic gene expression, and neuronal cell counts. The offspring from mothers switching to e-cigarettes exhibited no change in exploration/activity but showed a decrease in global DNA methylation, Aurora Kinase (Aurk) A and AurkB gene expression and a reduction in neuronal cell numbers in the cornu ammonis 1 region of the dorsal hippocampus compared with the SE group. Continuous tobacco cigarette smoke exposure during pregnancy resulted in marked neurological deficits in the offspring. Switching to e-cigarettes during pregnancy reduced these neurological deficits compared with cigarette smoke exposure. However, neurological changes were still observed, so we therefore conclude that e-cigarette use during pregnancy is not advised.

scholarly journals Cigarette smoke-induced oxidative stress alters DNA methylation patterns in sperm and neurological gene expression patterns in offspring

2019 ◽  
Vol 112 (3) ◽  
pp. e337
Author(s):  
Patrick J. Murphy ◽  
Jingtao Guo ◽  
Timothy G. Jenkins ◽  
John R. Hoidal ◽  
Thomas Huecksteadt ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Dna Methylation ◽  
Cigarette Smoke ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Methylation Patterns

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

Epigenomes ◽  
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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