Pathophysiological adaptations of resistance arteries in rat offspring exposed in
utero to maternal obesity is associated with sex-specific epigenetic alterations
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.
