Mice generated by in vitro fertilization exhibit vascular dysfunction and shortened life span

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

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Rexhaj, Emrush; Rimoldi, Stefano; Fuster, Daniel Guido; Anderegg, Manuel Andreas; Bouillet, Elisa; Allemann, Yves; Sartori, Claudio and Scherrer, Urs

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0021-9738

Publisher:

American Society for Clinical Investigation

Language:

English

Submitter:

Daniel Fuster

Date Deposited:

03 Mar 2014 09:45

Last Modified:

19 Jan 2016 16:14

Publisher DOI:

10.1172/JCI68943

PubMed ID:

24270419

BORIS DOI:

10.7892/boris.41108

URI:

https://boris.unibe.ch/id/eprint/41108

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