Prenatal air pollution exposure to diesel exhaust induces cardiometabolic disorders in adulthood in a sex-specific manner

Delphine Rousseau-Ralliard (1) , Christophe Richard (1) , Pauline Hoarau (1) , Marie-Sylvie Lallemand (1) , Lucie Morillon (1) , Marie-Christine Aubrière (1) , Sarah A Valentino (1) , Michèle Dahirel (1) , Marine Guinot (1) , Natalie Fournier (2) , Gwendoline Morin (3) , Eve Mourier (1) , Sylvaine Camous (1) , Rémy Slama (4) , Flemming R Cassee (5) , Anne Couturier-Tarrade (1) , Pascale Chavatte-Palmer (1)

1 BREED - Biologie de la Reproduction, Environnement, Epigénétique & Développement
2 Lip(Sys)² - Lipides : systèmes analytiques et biologiques
3 SAAJ - Sciences de l'Animal et de l'Aliment de Jouy
4 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
5 Universiteit Utrecht / Utrecht University [Utrecht]

Results from observational and experimental studies indicate that exposure to air pollutants during gestation reduces birth weight, whereas little is known on potential cardiometabolic consequences for the offspring at adulthood. Our aim was to evaluate the long-term effects of gestational exposure to diesel engine exhaust (DE) on adult offspring phenotype in a rabbit model. The protocol was designed to mimic human exposure in large European cities. Females rabbits were exposed to diluted (1 mg/m3) DE (exposed, n = 9) or clean air (controls, n = 7), from 3 days after mating, 2 h/d and 5 d/wk in a nose-only inhalation system throughout gestation (gestation days 3-27). After birth and weaning, 72 offspring (47 exposed and 25 controls) were raised until adulthood (7.5 months) to evaluate their cardio-metabolic status, including the monitoring of body weight and food intake, fasting biochemistry, body composition (iDXA), cardiovascular parameters and glucose tolerance. After a metabolic challenge (high fat diet in males and gestation in females), animals were euthanized for postmortem phenotyping. Sex-specific responses to maternal exposure were observed in adult offspring. Age-related increases in blood pressure (p = 0.058), glycaemia (p = 0.029), and perirenal fat mass (p = 0.026) as well as reductions in HDL-cholesterol (p = 0.025) and fat-to-body weight ratio (p = 0.011) were observed in exposed males, suggesting a metabolic syndrome. Almost only trends were observed in exposed females with higher triglycerides and decreased bone density compared to control females. Metabolic challenges triggered or amplified some biological responses, especially in females. In utero exposure to air pollution predisposed rabbit offspring to cardiometabolic disorders in a sex-specific manner.

Mots clés: Fetal programming; Adult offspring; diesel exhaust; Gestational exposure; Intergenerational effect; Rabbit biomedical model

Domaines: Sciences du Vivant [q-bio]; Santé publique et épidémiologie

Delphine Rousseau-Ralliard, Christophe Richard, Pauline Hoarau, Marie-Sylvie Lallemand, Lucie Morillon, et al.. Prenatal air pollution exposure to diesel exhaust induces cardiometabolic disorders in adulthood in a sex-specific manner. Environmental Research, 2021, 200, pp.111690. ⟨10.1016/j.envres.2021.111690⟩. ⟨hal-03312025⟩