Pathophysiological adaptations of resistance arteries in rat offspring exposed in utero to maternal obesity is associated with sex-specific epigenetic alterations
Abstract
Background/objectives Maternal obesity impacts vascular functions linked to metabolic disorders in offspring, leading to cardiovascular diseases during adulthood. Even if the relation between prenatal conditioning of cardiovascular diseases by maternal obesity and vascular function begins to be documented, little is known about resistance arteries. They are of particular interest because of their specific role in the regulation of local blood flow. Then our study aims to determine if maternal obesity can directly program fetal vascular dysfunction of resistance arteries, independently of metabolic disorders. Methods With a model of rats exposed in utero to mild maternal diet-induced obesity (OMO), we investigated third-order mesenteric arteries of 4-month old rats in absence of metabolic disorders. The methylation profile of these vessels was determined by reduced representation bisulfite sequencing (RRBS). Vascular structure and reactivity were investigated using histomorphometry analysis and wire-myography. The metabolic function was evaluated by insulin and glucose tolerance tests, plasma lipid profile, and adipose tissue analysis. Results At 4 months of age, small mesenteric arteries of OMO presented specific epigenetic modulations of matrix metalloproteinases (MMPs), collagens, and potassium channels genes in association with an outward remodeling and perturbations in the endothelium-dependent vasodilation pathways (greater contribution of EDHFs pathway in OMO males compared to control rats, and greater implication of PGI 2 in OMO females compared to control rats). These vascular modifications were detected in absence of metabolic disorders. Conclusions Our study reports a specific methylation profile of resistance arteries associated with vascular remodeling and vasodilation balance perturbations in offspring exposed in utero to maternal obesity, in absence of metabolic dysfunctions.
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Several studies have reported impaired vascular function between three and six months of age in arteries isolated from rat offspring of obese dams.
“Several studies have reported elevated blood pressure as well as vascular remodeling and impaired vascular function between three and six months of age in arteries isolated from rat offspring of obese dams [94,100,126,127].”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [127]
Several studies have reported elevated blood pressure between three and six months of age in arteries isolated from rat offspring of obese dams.
“Several studies have reported elevated blood pressure as well as vascular remodeling and impaired vascular function between three and six months of age in arteries isolated from rat offspring of obese dams [94,100,126,127].”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [127]
Several studies have reported vascular remodeling between three and six months of age in arteries isolated from rat offspring of obese dams.
“Several studies have reported elevated blood pressure as well as vascular remodeling and impaired vascular function between three and six months of age in arteries isolated from rat offspring of obese dams [94,100,126,127].”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [127]
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- Authors
- Payen, C., Guillot, A., Paillat, L., Fothi, A., Dib, A., Bourreau, J., Schmitt, F., Loufrani, L., Aranyi, T., Henrion, D., Munier, M., & Fassot, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Université d'Angers (FR)
- Corresponding author
- Fassot, Céline
- ORCID
- Venue
- International Journal of Obesity
- Published
- 2021-02-26
- Volume
- 45
- Issue
- 5
- Pages
- 1074-1085
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- OpenAlex
- W3129824578
- Cited by
- 12
- References
- 50
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 1 · 2022: 4 · 2021: 1
- FWCI
- 2.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- maternal obesity, prenatal programming, resistance arteries, mesenteric arteries, DNA methylation, epigenetics, sex differences, vascular remodeling, endothelium-dependent vasodilation, matrix metalloproteinases, collagen, potassium channels, diet-induced obesity
- MeSH terms
- Obesity, Maternal, Pregnancy in Obesity, Animals, Collagen, Endothelium, Vascular, Female, Male, Pregnancy, Prenatal Exposure Delayed Effects, Sex Factors, Vascular Resistance, Potassium Channels, Rats, Sprague-Dawley, DNA Methylation, Matrix Metalloproteinases, Epigenesis, Genetic, Rats, Diet, High-Fat
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