Counteracting Environmental Chemicals with Coenzyme Q10: An Educational Primer for Use with “Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline”

Environmental toxicants are chemicals that negatively affect human health. Although there are numerous ways to limit exposure, the ubiquitous nature of certain environmental toxicants makes it impossible to avoid them entirely. Consequently, scientists are continuously working toward developing strategies for combating their harmful effects. Using the nematode Caenorhabditis elegans, a model with many genetic and physiological similarities to humans, researchers in the Colaiácovo laboratory have identified several molecular mechanisms by which the toxic agent bisphenol A (BPA) interferes with reproduction. Here, we address their recent discovery that a widely available compound, Coenzyme Q10 (CoQ10), can rescue BPA-induced damage. This work is significant in that it poses a low-cost method for improving reproductive success in humans. The goal of this primer is to assist educators and students with navigating the paper entitled “Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline.” It is ideally suited for integration into an upper-level undergraduate course such as Genetics, Cell and Molecular Biology, Developmental Biology, or Toxicology. The primer provides background information on the history of BPA, the utility of the C. elegans germ line as a model for studying reproductive toxicity, and research methods including assessment of programmed cell death, fluorescent microscopy applications, and assays to quantify gene expression. Questions for deeper exploration in-class or online are provided.Related article in GENETICS: Hornos Carneiro MF, Shin N, Karthikraj R, Barbosa F Jr, Kannan K, Colaiácovo MP. Antioxidant CoQ10 restores fertility by rescuing bisphenol A-induced oxidative DNA damage in the Caenorhabditis elegans Germline. Genetics 214:381–395.

Download Full-text

Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline

Genetics ◽

10.1534/genetics.119.302939 ◽

2019 ◽

Vol 214 (2) ◽

pp. 381-395 ◽

Cited By ~ 6

Author(s):

Maria Fernanda Hornos Carneiro ◽

Nara Shin ◽

Rajendiran Karthikraj ◽

Fernando Barbosa ◽

Kurunthachalam Kannan ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Caenorhabditis Elegans ◽

Bisphenol A ◽

Oxidative Dna Damage ◽

Low Cost ◽

Endocrine Disrupting Chemicals ◽

Human Reproductive ◽

Low Cost Strategy ◽

The Impact

Endocrine-disrupting chemicals are ubiquitously present in our environment, but the mechanisms by which they adversely affect human reproductive health and strategies to circumvent their effects remain largely unknown. Here, we show in Caenorhabditis elegans that supplementation with the antioxidant Coenzyme Q10 (CoQ10) rescues the reprotoxicity induced by the widely used plasticizer and endocrine disruptor bisphenol A (BPA), in part by neutralizing DNA damage resulting from oxidative stress. CoQ10 significantly reduces BPA-induced elevated levels of germ cell apoptosis, phosphorylated checkpoint kinase 1 (CHK-1), double-strand breaks (DSBs), and chromosome defects in diakinesis oocytes. BPA-induced oxidative stress, mitochondrial dysfunction, and increased gene expression of antioxidant enzymes in the germline are counteracted by CoQ10. Finally, CoQ10 treatment also reduced the levels of aneuploid embryos and BPA-induced defects observed in early embryonic divisions. We propose that CoQ10 may counteract BPA-induced reprotoxicity through the scavenging of reactive oxygen species and free radicals, and that this natural antioxidant could constitute a low-risk and low-cost strategy to attenuate the impact on fertility by BPA.

Download Full-text

Molecular Mechanisms of Zinc Oxide Nanoparticle-Induced Genotoxicity

Materials ◽

10.3390/ma10121427 ◽

2017 ◽

Vol 10 (12) ◽

pp. 1427 ◽

Cited By ~ 25

Author(s):

Agmal Scherzad ◽

Till Meyer ◽

Norbert Kleinsasser ◽

Stephan Hackenberg

Keyword(s):

Dna Damage ◽

Zinc Oxide ◽

Mammalian Cells ◽

Oxidative Dna Damage ◽

Molecular Mechanisms ◽

Consumer Products ◽

Zno Nps ◽

Cytotoxic Effects

Background: Zinc oxide nanoparticles (ZnO NPs) are among the most frequently applied nanomaterials in consumer products. Evidence exists regarding the cytotoxic effects of ZnO NPs in mammalian cells; however, knowledge about the potential genotoxicity of ZnO NPs is rare, and results presented in the current literature are inconsistent. Objectives: The aim of this review is to summarize the existing data regarding the DNA damage that ZnO NPs induce, and focus on the possible molecular mechanisms underlying genotoxic events. Methods: Electronic literature databases were systematically searched for studies that report on the genotoxicity of ZnO NPs. Results: Several methods and different endpoints demonstrate the genotoxic potential of ZnO NPs. Most publications describe in vitro assessments of the oxidative DNA damage triggered by dissoluted Zn2+ ions. Most genotoxicological investigations of ZnO NPs address acute exposure situations. Conclusion: Existing evidence indicates that ZnO NPs possibly have the potential to damage DNA. However, there is a lack of long-term exposure experiments that clarify the intracellular bioaccumulation of ZnO NPs and the possible mechanisms of DNA repair and cell survival.

Download Full-text

In vivo repair of alkylating and oxidative DNA damage in the mitochondrial and nuclear genomes of wild-type and glycosylase-deficient Caenorhabditis elegans

DNA Repair ◽

10.1016/j.dnarep.2012.08.002 ◽

2012 ◽

Vol 11 (11) ◽

pp. 857-863 ◽

Cited By ~ 15

Author(s):

Senyene E. Hunter ◽

Margaret A. Gustafson ◽

Kathleen M. Margillo ◽

Sean A. Lee ◽

Ian T. Ryde ◽

...

Keyword(s):

Dna Damage ◽

Caenorhabditis Elegans ◽

Oxidative Dna Damage ◽

Wild Type ◽

Nuclear Genomes

Download Full-text

Paternal impacts on development: identification of genomic regions vulnerable to oxidative DNA damage in human spermatozoa

Human Reproduction ◽

10.1093/humrep/dez153 ◽

2019 ◽

Vol 34 (10) ◽

pp. 1876-1890 ◽

Cited By ~ 8

Author(s):

M J Xavier ◽

B Nixon ◽

S D Roman ◽

R J Scott ◽

J R Drevet ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Male Infertility ◽

Oxidative Damage ◽

Oxidative Dna Damage ◽

Human Spermatozoa ◽

Research Centre ◽

Environmental Toxicants ◽

Next Generation ◽

Genomic Regions

Abstract STUDY QUESTION Do all regions of the paternal genome within the gamete display equivalent vulnerability to oxidative DNA damage? SUMMARY ANSWER Oxidative DNA damage is not randomly distributed in mature human spermatozoa but is instead targeted, with particular chromosomes being especially vulnerable to oxidative stress. WHAT IS KNOWN ALREADY Oxidative DNA damage is frequently encountered in the spermatozoa of male infertility patients. Such lesions can influence the incidence of de novo mutations in children, yet it remains to be established whether all regions of the sperm genome display equivalent susceptibility to attack by reactive oxygen species. STUDY DESIGN, SIZE, DURATION Human spermatozoa obtained from normozoospermic males (n = 8) were split into equivalent samples and subjected to either hydrogen peroxide (H2O2) treatment or vehicle controls before extraction of oxidized DNA using a modified DNA immunoprecipitation (MoDIP) protocol. Specific regions of the genome susceptible to oxidative damage were identified by next-generation sequencing and validated in the spermatozoa of normozoospermic males (n = 18) and in patients undergoing infertility evaluation (n = 14). PARTICIPANTS/MATERIALS, SETTING, METHODS Human spermatozoa were obtained from normozoospermic males and divided into two identical samples prior to being incubated with either H2O2 (5 mm, 1 h) to elicit oxidative stress or an equal volume of vehicle (untreated controls). Alternatively, spermatozoa were obtained from fertility patients assessed as having high basal levels of oxidative stress within their spermatozoa. All semen samples were subjected to MoDIP to selectively isolate oxidized DNA, prior to sequencing of the resultant DNA fragments using a next-generation whole-genomic sequencing platform. Bioinformatic analysis was then employed to identify genomic regions vulnerable to oxidative damage, several of which were selected for real-time quantitative PCR (qPCR) validation. MAIN RESULTS AND THE ROLE OF CHANCE Approximately 9000 genomic regions, 150–1000 bp in size, were identified as highly vulnerable to oxidative damage in human spermatozoa. Specific chromosomes showed differential susceptibility to damage, with chromosome 15 being particularly sensitive to oxidative attack while the sex chromosomes were protected. Susceptible regions generally lay outside protamine- and histone-packaged domains. Furthermore, we confirmed that these susceptible genomic sites experienced a dramatic (2–15-fold) increase in their burden of oxidative DNA damage in patients undergoing infertility evaluation compared to normal healthy donors. LIMITATIONS, REASONS FOR CAUTION The limited number of samples analysed in this study warrants external validation, as do the implications of our findings. Selection of male fertility patients was based on high basal levels of oxidative stress within their spermatozoa as opposed to specific sub-classes of male factor infertility. WIDER IMPLICATIONS OF THE FINDINGS The identification of genomic regions susceptible to oxidation in the male germ line will be of value in focusing future analyses into the mutational load carried by children in response to paternal factors such as age, the treatment of male infertility using ART and paternal exposure to environmental toxicants. STUDY FUNDING/COMPETING INTEREST(S) Project support was provided by the University of Newcastle’s (UoN) Priority Research Centre for Reproductive Science. M.J.X. was a recipient of a UoN International Postgraduate Research Scholarship. B.N. is the recipient of a National Health and Medical Research Council of Australia Senior Research Fellowship. Authors declare no conflict of interest.

Download Full-text

Correlations between Oxidative DNA Damage, Oxidative Stress and Coenzyme Q10 in Patients with Coronary Artery Disease

International Journal of Medical Sciences ◽

10.7150/ijms.4768 ◽

2012 ◽

Vol 9 (8) ◽

pp. 621-626 ◽

Cited By ~ 28

Author(s):

Yüksel KAYA ◽

Ayşegül ÇEBİ ◽

Nihat SÖYLEMEZ ◽

Halit DEMİR ◽

Hamit Hakan ALP ◽

...

Keyword(s):

Oxidative Stress ◽

Coronary Artery Disease ◽

Dna Damage ◽

Coronary Artery ◽

Coenzyme Q10 ◽

Oxidative Dna Damage ◽

Artery Disease

Download Full-text

Genomic landscape of oxidative DNA damage and repair reveals regioselective protection from mutagenesis

10.1101/168153 ◽

2017 ◽

Cited By ~ 1

Author(s):

Anna R Poetsch ◽

Simon J Boulton ◽

Nicholas M Luscombe

Keyword(s):

Dna Damage ◽

Oxidative Damage ◽

Oxidative Dna Damage ◽

Molecular Mechanisms ◽

Accumulation Rate ◽

Repetitive Sequences ◽

Open Chromatin ◽

Regulatory Sequences ◽

Dna Damage And Repair ◽

A Genome

AbstractDNA is subject to constant chemical modification and damage, which eventually results in variable mutation rates throughout the genome. Although detailed molecular mechanisms of DNA damage and repair are well-understood, damage impact and execution of repair across a genome remains poorly defined. To bridge the gap between our understanding of DNA repair and mutation distributions we developed a novel method, AP-seq, capable of mapping apurinic sitesand 8-oxo-7,8-dihydroguanine bases at ∼300bp resolution on a genome-wide scale. We directly demonstrate that the accumulation rate of oxidative damage varies widely across the genome, with hot spots acquiring many times more damage than cold spots. Unlike SNVs in cancers, damage burden correlates with marks for open chromatin notably H3K9ac and H3K4me2. Oxidative damage is also highly enriched in transposable elements and other repetitive sequences. In contrast, we observe decreased damage at promoters, exons and termination sites, but not introns, in a seemingly transcription-independent manner. Leveraging cancer genomic data, we also find locally reduced SNV rates in promoters, genes and other functional elements. Taken together, our study reveals that oxidative DNA damage accumulation and repair differ strongly across the genome, but culminate in a previously unappreciated mechanism that safe-guards the regulatory sequences and the coding regions of genes from mutations.

Download Full-text