Prevention of vascular dysfunction and arterial hypertension in mice generated by assisted reproductive technologies by addition of melatonin to culture media
| Autor: | Urs Scherrer, Pierre Dessen, Emrush Rexhaj, David Cerny, Stefano F. Rimoldi, Yves Allemann, Agim Pireva, Ariane Paoloni-Giacobino, Claudio Sartori |
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| Rok vydání: | 2015 |
| Předmět: |
Physiology
Vasodilator Agents Blood Pressure Reproductive technology Antioxidants Epigenesis Genetic Embryo Culture Techniques chemistry.chemical_compound Mice Enos ddc:576.5 Nitric Oxide Synthase Type III/drug effects/genetics Endothelial dysfunction Promoter Regions Genetic Vascular tissue Melatonin Acetylcholine/pharmacology biology Nitric Oxide Synthase Type III DNA Methylation/drug effects Mesenteric Arteries Hypertension Mesenteric Arteries/drug effects Cardiology and Cardiovascular Medicine medicine.drug medicine.medical_specialty Reproductive Techniques Assisted Melatonin/pharmacology Nitric Oxide Epigenesis Genetic/drug effects Blood Pressure/drug effects Nitric oxide Physiology (medical) Internal medicine medicine Animals Vasodilator Agents/pharmacology Promoter Regions Genetic/drug effects DNA Methylation biology.organism_classification medicine.disease Acetylcholine Culture Media Endocrinology Blood pressure Hypertension/prevention & control chemistry Antioxidants/pharmacology Nitric Oxide/metabolism |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology American Journal of Physiology. Heart and Circulatory Physiology, Vol. 309, No 7 (2015) pp. H1151-H1156 AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY |
| ISSN: | 0363-6135 |
| DOI: | 10.1152/ajpheart.00621.2014 |
| Popis: | Assisted reproductive technologies (ART) induce vascular dysfunction in humans and mice. In mice, ART-induced vascular dysfunction is related to epigenetic alteration of the endothelial nitric oxide synthase (eNOS) gene, resulting in decreased vascular eNOS expression and nitrite/nitrate synthesis. Melatonin is involved in epigenetic regulation, and its administration to sterile women improves the success rate of ART. We hypothesized that addition of melatonin to culture media may prevent ART-induced epigenetic and cardiovascular alterations in mice. We, therefore, assessed mesenteric-artery responses to acetylcholine and arterial blood pressure, together with DNA methylation of the eNOS gene promoter in vascular tissue and nitric oxide plasma concentration in 12-wk-old ART mice generated with and without addition of melatonin to culture media and in control mice. As expected, acetylcholine-induced mesenteric-artery dilation was impaired ( P = 0.008 vs. control) and mean arterial blood pressure increased (109.5 ± 3.8 vs. 104.0 ± 4.7 mmHg, P = 0.002, ART vs. control) in ART compared with control mice. These alterations were associated with altered DNA methylation of the eNOS gene promoter ( P < 0.001 vs. control) and decreased plasma nitric oxide concentration (10.1 ± 11.1 vs. 29.5 ± 8.0 μM) ( P < 0.001 ART vs. control). Addition of melatonin (10−6 M) to culture media prevented eNOS dysmethylation ( P = 0.005, vs. ART + vehicle), normalized nitric oxide plasma concentration (23.1 ± 14.6 μM, P = 0.002 vs. ART + vehicle) and mesentery-artery responsiveness to acetylcholine ( P < 0.008 vs. ART + vehicle), and prevented arterial hypertension (104.6 ± 3.4 mmHg, P < 0.003 vs. ART + vehicle). These findings provide proof of principle that modification of culture media prevents ART-induced vascular dysfunction. We speculate that this approach will also allow preventing ART-induced premature atherosclerosis in humans. |
| Databáze: | OpenAIRE |
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