A novel antioxidant formulation designed to treat male infertility associated with oxidative stress: promising preclinical evidence from animal models.
Identifieur interne : 002F44 ( Ncbi/Merge ); précédent : 002F43; suivant : 002F45A novel antioxidant formulation designed to treat male infertility associated with oxidative stress: promising preclinical evidence from animal models.
Auteurs : P. Gharagozloo [Oman] ; A. Gutiérrez-Adán [Espagne] ; A. Champroux [France] ; A. Noblanc [France] ; A. Kocer [France] ; A. Calle [Espagne] ; S. Pérez-Cerezales [Espagne] ; E. Pericuesta [Espagne] ; A. Polhemus [États-Unis] ; A. Moazamian [États-Unis] ; J R Drevet [France] ; R J Aitken [Australie]Source :
- Human reproduction (Oxford, England) [ 1460-2350 ] ; 2016.
Descripteurs français
- KwdFr :
- Altération de l'ADN, Analyse du sperme, Animaux, Antioxydants (pharmacologie), Désoxyguanosine (analogues et dérivés), Désoxyguanosine (métabolisme), Femelle, Glutathione peroxidase (génétique), Grossesse, Infertilité masculine (génétique), Infertilité masculine (traitement médicamenteux), Issue de la grossesse, Marqueurs biologiques (métabolisme), Modèles animaux, Mâle, Souris, Souris de lignée C57BL, Souris knockout, Spermatozoïdes (), Spermatozoïdes (métabolisme), Stress oxydatif, Taux de grossesse.
- MESH :
- analogues et dérivés : Désoxyguanosine.
- génétique : Glutathione peroxidase, Infertilité masculine.
- métabolisme : Désoxyguanosine, Marqueurs biologiques, Spermatozoïdes.
- pharmacologie : Antioxydants.
- traitement médicamenteux : Infertilité masculine.
- Altération de l'ADN, Analyse du sperme, Animaux, Femelle, Grossesse, Issue de la grossesse, Modèles animaux, Mâle, Souris, Souris de lignée C57BL, Souris knockout, Spermatozoïdes, Stress oxydatif, Taux de grossesse.
English descriptors
- KwdEn :
- Animals, Antioxidants (pharmacology), Biomarkers (metabolism), DNA Damage, Deoxyguanosine (analogs & derivatives), Deoxyguanosine (metabolism), Female, Glutathione Peroxidase (genetics), Infertility, Male (drug therapy), Infertility, Male (genetics), Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Animal, Oxidative Stress, Pregnancy, Pregnancy Outcome, Pregnancy Rate, Semen Analysis, Spermatozoa (drug effects), Spermatozoa (metabolism).
- MESH :
- chemical , analogs & derivatives : Deoxyguanosine.
- chemical , genetics : Glutathione Peroxidase.
- chemical , metabolism : Biomarkers, Deoxyguanosine.
- chemical , pharmacology : Antioxidants.
- drug effects : Spermatozoa.
- drug therapy : Infertility, Male.
- genetics : Infertility, Male.
- metabolism : Spermatozoa.
- Animals, DNA Damage, Female, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Animal, Oxidative Stress, Pregnancy, Pregnancy Outcome, Pregnancy Rate, Semen Analysis.
Abstract
Does a novel antioxidant formulation designed to restore redox balance within the male reproductive tract, reduce sperm DNA damage and increase pregnancy rates in mouse models of sperm oxidative stress?
DOI: 10.1093/humrep/dev302
PubMed: 26732620
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 002309
- to stream PubMed, to step Curation: 002283
- to stream PubMed, to step Checkpoint: 002283
Links to Exploration step
pubmed:26732620Le document en format XML
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<front><div type="abstract" xml:lang="en">Does a novel antioxidant formulation designed to restore redox balance within the male reproductive tract, reduce sperm DNA damage and increase pregnancy rates in mouse models of sperm oxidative stress?</div>
</front>
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<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26732620</PMID>
<DateCreated><Year>2016</Year>
<Month>01</Month>
<Day>19</Day>
</DateCreated>
<DateCompleted><Year>2016</Year>
<Month>11</Month>
<Day>04</Day>
</DateCompleted>
<DateRevised><Year>2016</Year>
<Month>12</Month>
<Day>30</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1460-2350</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>31</Volume>
<Issue>2</Issue>
<PubDate><Year>2016</Year>
<Month>Feb</Month>
</PubDate>
</JournalIssue>
<Title>Human reproduction (Oxford, England)</Title>
<ISOAbbreviation>Hum. Reprod.</ISOAbbreviation>
</Journal>
<ArticleTitle>A novel antioxidant formulation designed to treat male infertility associated with oxidative stress: promising preclinical evidence from animal models.</ArticleTitle>
<Pagination><MedlinePgn>252-62</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1093/humrep/dev302</ELocationID>
<Abstract><AbstractText Label="STUDY QUESTION" NlmCategory="OBJECTIVE">Does a novel antioxidant formulation designed to restore redox balance within the male reproductive tract, reduce sperm DNA damage and increase pregnancy rates in mouse models of sperm oxidative stress?</AbstractText>
<AbstractText Label="SUMMARY ANSWER" NlmCategory="CONCLUSIONS">Oral administration of a novel antioxidant formulation significantly reduced sperm DNA damage in glutathione peroxidase 5 (GPX5), knockout mice and restored pregnancy rates to near-normal levels in mice subjected to scrotal heat stress.</AbstractText>
<AbstractText Label="WHAT IS KNOWN ALREADY" NlmCategory="BACKGROUND">Animal and human studies have documented the adverse effect of sperm DNA damage on fertilization rates, embryo quality, miscarriage rates and the transfer of de novo mutations to offspring. Semen samples of infertile men are known to be deficient in several key antioxidants relative to their fertile counterparts. Antioxidants alone or in combination have demonstrated limited efficacy against sperm oxidative stress and DNA damage in numerous human clinical trials, however these studies have not been definitive and an optimum combination has remained elusive.</AbstractText>
<AbstractText Label="STUDY DESIGN, SIZE, DURATION" NlmCategory="METHODS">The efficacy of the antioxidant formulation was evaluated in two well-established mouse models of oxidative stress, scrotal heating and Gpx5 knockout (KO) mice, (n = 12 per experimental group), by two independent laboratories. Mice were provided the antioxidant product in their drinking water for 2-8 weeks and compared with control groups for sperm DNA damage and pregnancy rates.</AbstractText>
<AbstractText Label="PARTICIPANTS/MATERIALS, SETTING, METHODS" NlmCategory="METHODS">In the Gpx5 KO model, oxidative DNA damage was monitored in spermatozoa by immunocytochemical detection of 8-hydroxy-2'-deoxyguanosine (8OHdG). In the scrotal heat stress model, male fertility was tested by partnering with three females for 5 days. The percentage of pregnant females, number of vaginal plugs, resorptions per litter, and litter size were recorded.</AbstractText>
<AbstractText Label="MAIN RESULTS AND ROLE OF CHANCE" NlmCategory="RESULTS">Using immunocytochemical detection of 8OHdG as a biomarker of DNA oxidation, analysis of control mice revealed that around 30% of the sperm population was positively stained. This level increased to about 60% in transgenic mice deficient in the antioxidant enzyme, GPX5. Our results indicate that an 8 week pretreatment of Gpx5 KO mice with the antioxidant formulation provided complete protection of sperm DNA against oxidative damage. In mouse models of scrotal heat stress, only 35% (19/54) of female mice became pregnant resulting in 169 fetuses with 18% fetal resorption (30/169). This is in contrast to the antioxidant pretreated group where 74% (42/57) of female mice became pregnant, resulting in 427 fetuses with 9% fetal resorption (38/427). In both animal models the protection provided by the novel antioxidant was statistically significant (P < 0.01 for the reduction of 8OHdG in the spermatozoa of Gpx5 KO mice and P < 0.05 for increase in fertility in the scrotal heat stress model).</AbstractText>
<AbstractText Label="LIMITATIONS, REASONS FOR CAUTION" NlmCategory="CONCLUSIONS">It was not possible to determine the exact level of antioxidant consumption for each mouse during the treatment period.</AbstractText>
<AbstractText Label="WIDER IMPLICATIONS OF THE FINDINGS" NlmCategory="CONCLUSIONS">Recent clinical studies confirm moderate to severe sperm DNA damage in about 60% of all men visiting IVF centers and in about 80% of men diagnosed with idiopathic male infertility. Our results, if confirmed in humans, will impact clinical fertility practice because they support the concept of using an efficacious antioxidant supplementation as a preconception therapy, in order to optimize fertilization rates, help to maintain a healthy pregnancy and limit the mutational load carried by children.</AbstractText>
<AbstractText Label="STUDY FUNDING/COMPETING INTERESTS" NlmCategory="BACKGROUND">The study was funded by the Clermont Université and the University of Madrid. P.G. is the Managing Director of CellOxess LLC, which has a commercial interest in the detection and resolution of oxidative stress. A.M. and A.P. are employees of CellOxess, LLC. J.R.D., A.G.-A. and R.J.A. are honorary members of the CellOxess advisory board.</AbstractText>
<CopyrightInformation>© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gharagozloo</LastName>
<ForeName>P</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>CellOxess LLC, 15 Roszel Road, Princeton, NJ 08540, USA parviz.gharagozloo@celloxess.com.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gutiérrez-Adán</LastName>
<ForeName>A</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>INIA, Animal Reproduction, Madrid 28040, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Champroux</LastName>
<ForeName>A</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>GReD Lab CNRS UMR6293-INSERM U1103 Université Blaise Pascal-Clermont II, Clermont-Ferrand 63001, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Noblanc</LastName>
<ForeName>A</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>GReD Lab CNRS UMR6293-INSERM U1103 Université Blaise Pascal-Clermont II, Clermont-Ferrand 63001, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kocer</LastName>
<ForeName>A</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>GReD Lab CNRS UMR6293-INSERM U1103 Université Blaise Pascal-Clermont II, Clermont-Ferrand 63001, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Calle</LastName>
<ForeName>A</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>INIA, Animal Reproduction, Madrid 28040, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pérez-Cerezales</LastName>
<ForeName>S</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>INIA, Animal Reproduction, Madrid 28040, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pericuesta</LastName>
<ForeName>E</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>INIA, Animal Reproduction, Madrid 28040, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Polhemus</LastName>
<ForeName>A</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>CellOxess LLC, 15 Roszel Road, Princeton, NJ 08540, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Moazamian</LastName>
<ForeName>A</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>CellOxess LLC, 15 Roszel Road, Princeton, NJ 08540, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Drevet</LastName>
<ForeName>J R</ForeName>
<Initials>JR</Initials>
<AffiliationInfo><Affiliation>GReD Lab CNRS UMR6293-INSERM U1103 Université Blaise Pascal-Clermont II, Clermont-Ferrand 63001, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Aitken</LastName>
<ForeName>R J</ForeName>
<Initials>RJ</Initials>
<AffiliationInfo><Affiliation>Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia The University of Newcastle, University Drive, Callaghan, NSW 2308, Australia.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2016</Year>
<Month>01</Month>
<Day>04</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>England</Country>
<MedlineTA>Hum Reprod</MedlineTA>
<NlmUniqueID>8701199</NlmUniqueID>
<ISSNLinking>0268-1161</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000975">Antioxidants</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D015415">Biomarkers</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>88847-89-6</RegistryNumber>
<NameOfSubstance UI="C067134">8-oxo-7-hydrodeoxyguanosine</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 1.11.1.9</RegistryNumber>
<NameOfSubstance UI="D005979">Glutathione Peroxidase</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 1.11.1.9</RegistryNumber>
<NameOfSubstance UI="C080439">selenium-independent glutathione peroxidase</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>G9481N71RO</RegistryNumber>
<NameOfSubstance UI="D003849">Deoxyguanosine</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000975" MajorTopicYN="N">Antioxidants</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015415" MajorTopicYN="N">Biomarkers</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004249" MajorTopicYN="N">DNA Damage</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003849" MajorTopicYN="N">Deoxyguanosine</DescriptorName>
<QualifierName UI="Q000031" MajorTopicYN="N">analogs & derivatives</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005979" MajorTopicYN="N">Glutathione Peroxidase</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007248" MajorTopicYN="N">Infertility, Male</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018345" MajorTopicYN="N">Mice, Knockout</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D023421" MajorTopicYN="N">Models, Animal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018384" MajorTopicYN="Y">Oxidative Stress</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011247" MajorTopicYN="N">Pregnancy</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011256" MajorTopicYN="N">Pregnancy Outcome</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018873" MajorTopicYN="N">Pregnancy Rate</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D055101" MajorTopicYN="N">Semen Analysis</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013094" MajorTopicYN="N">Spermatozoa</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">antioxidants</Keyword>
<Keyword MajorTopicYN="N">glutathione peroxidase 5</Keyword>
<Keyword MajorTopicYN="N">infertility</Keyword>
<Keyword MajorTopicYN="N">oxidative stress</Keyword>
<Keyword MajorTopicYN="N">reactive oxygen species</Keyword>
<Keyword MajorTopicYN="N">scrotal heat stress</Keyword>
<Keyword MajorTopicYN="N">sperm DNA damage</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year>
<Month>07</Month>
<Day>25</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2015</Year>
<Month>11</Month>
<Day>09</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2016</Year>
<Month>1</Month>
<Day>7</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2016</Year>
<Month>1</Month>
<Day>7</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<PubMedPubDate PubStatus="medline"><Year>2016</Year>
<Month>11</Month>
<Day>5</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">26732620</ArticleId>
<ArticleId IdType="pii">dev302</ArticleId>
<ArticleId IdType="doi">10.1093/humrep/dev302</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>Australie</li>
<li>Espagne</li>
<li>France</li>
<li>Oman</li>
<li>États-Unis</li>
</country>
<region><li>Auvergne (région administrative)</li>
<li>Auvergne-Rhône-Alpes</li>
<li>Communauté de Madrid</li>
<li>New Jersey</li>
</region>
<settlement><li>Madrid</li>
</settlement>
</list>
<tree><country name="Oman"><noRegion><name sortKey="Gharagozloo, P" sort="Gharagozloo, P" uniqKey="Gharagozloo P" first="P" last="Gharagozloo">P. Gharagozloo</name>
</noRegion>
</country>
<country name="Espagne"><region name="Communauté de Madrid"><name sortKey="Gutierrez Adan, A" sort="Gutierrez Adan, A" uniqKey="Gutierrez Adan A" first="A" last="Gutiérrez-Adán">A. Gutiérrez-Adán</name>
</region>
<name sortKey="Calle, A" sort="Calle, A" uniqKey="Calle A" first="A" last="Calle">A. Calle</name>
<name sortKey="Perez Cerezales, S" sort="Perez Cerezales, S" uniqKey="Perez Cerezales S" first="S" last="Pérez-Cerezales">S. Pérez-Cerezales</name>
<name sortKey="Pericuesta, E" sort="Pericuesta, E" uniqKey="Pericuesta E" first="E" last="Pericuesta">E. Pericuesta</name>
</country>
<country name="France"><noRegion><name sortKey="Champroux, A" sort="Champroux, A" uniqKey="Champroux A" first="A" last="Champroux">A. Champroux</name>
</noRegion>
<name sortKey="Drevet, J R" sort="Drevet, J R" uniqKey="Drevet J" first="J R" last="Drevet">J R Drevet</name>
<name sortKey="Kocer, A" sort="Kocer, A" uniqKey="Kocer A" first="A" last="Kocer">A. Kocer</name>
<name sortKey="Noblanc, A" sort="Noblanc, A" uniqKey="Noblanc A" first="A" last="Noblanc">A. Noblanc</name>
</country>
<country name="États-Unis"><region name="New Jersey"><name sortKey="Polhemus, A" sort="Polhemus, A" uniqKey="Polhemus A" first="A" last="Polhemus">A. Polhemus</name>
</region>
<name sortKey="Moazamian, A" sort="Moazamian, A" uniqKey="Moazamian A" first="A" last="Moazamian">A. Moazamian</name>
</country>
<country name="Australie"><noRegion><name sortKey="Aitken, R J" sort="Aitken, R J" uniqKey="Aitken R" first="R J" last="Aitken">R J Aitken</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>
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