Mice generated by in vitro fertilization exhibit vascular dysfunction and shortened life span
| Autor: | Emmanuel Somm, Claudio Sartori, Stefano F. Rimoldi, Yves Allemann, Manuel Anderegg, Emrush Rexhaj, Daniel Guido Fuster, Ariane Paoloni-Giacobino, Elisa Bouillet, Urs Scherrer |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Vasodilation Reproductive technology Mice 0302 clinical medicine Enos ddc:576.5 Cardiovascular Abnormalities/embryology/etiology Endothelial dysfunction 610 Medicine & health Promoter Regions Genetic Aorta 0303 health sciences 030219 obstetrics & reproductive medicine Vasodilation/physiology Gene Expression Regulation Developmental Embryo General Medicine Butyrates medicine.anatomical_structure Hypertension DNA methylation Ovulation Induction/adverse effects Female Disease Susceptibility Histone Deacetylase Inhibitors/pharmacology/therapeutic use Cell Membrane/metabolism Epidermis/cytology Epidermis/metabolism Humans Keratins/metabolism Lactoperoxidase Membrane Proteins/metabolism Peptides/metabolism Psoriasis/metabolism Trypsin Research Article medicine.medical_specialty Nitric Oxide Synthase Type III Aorta/enzymology Nitric Oxide Synthase Type III/biosynthesis/genetics/physiology Cardiovascular Abnormalities Longevity Down-Regulation Fertilization in Vitro Biology Nitric Oxide Gene Expression Regulation Enzymologic 03 medical and health sciences Butyrates/pharmacology/therapeutic use Ovulation Induction Internal medicine medicine Animals Epigenetics 030304 developmental biology Endothelium Vascular/embryology/physiopathology Fertilization in Vitro/adverse effects/methods DNA Methylation medicine.disease biology.organism_classification Histone Deacetylase Inhibitors Endocrinology Nitric Oxide/metabolism Hypertension/embryology/etiology/physiopathology Vascular resistance 570 Life sciences biology Diet Atherogenic Vascular Resistance Endothelium Vascular Vascular Resistance/physiology |
| Zdroj: | Journal of Clinical Investigation Rexhaj, Emrush; Paoloni-Giacobino, Ariane; Rimoldi, Stefano F.; Fuster, Daniel Guido; Anderegg, Manuel; Somm, Emmanuel; Bouillet, Elisa; Allemann, Yves; Sartori, Claudio; Scherrer, Urs (2013). Mice generated by in vitro fertilization exhibit vascular dysfunction and shortened life span. Journal of clinical investigation, 123(12), pp. 5052-5060. American Society for Clinical Investigation 10.1172/JCI68943 Journal of Clinical Investigation, Vol. 123, No 12 (2013) pp. 5052-60 Journal of Clinical Investigation, vol. 123, no. 12, pp. 5052-5060 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/JCI68943 |
| Popis: | Children conceived by assisted reproductive technologies (ART) display a level of vascular dysfunction similar to that seen in children of mothers with preeclamspia. The long-term consequences of ART-associated vascular disorders are unknown and difficult to investigate in healthy children. Here, we found that vasculature from mice generated by ART display endothelial dysfunction and increased stiffness, which translated into arterial hypertension in vivo. Progeny of male ART mice also exhibited vascular dysfunction, suggesting underlying epigenetic modifications. ART mice had altered methylation at the promoter of the gene encoding eNOS in the aorta, which correlated with decreased vascular eNOS expression and NO synthesis. Administration of a deacetylase inhibitor to ART mice normalized vascular gene methylation and function and resulted in progeny without vascular dysfunction. The induction of ART-associated vascular and epigenetic alterations appeared to be related to the embryo environment; these alterations were possibly facilitated by the hormonally stimulated ovulation accompanying ART. Finally, ART mice challenged with a high-fat diet had roughly a 25% shorter life span compared with control animals. This study highlights the potential of ART to induce vascular dysfunction and shorten life span and suggests that epigenetic alterations contribute to these problems. |
| Databáze: | OpenAIRE |
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