TY - JOUR
T1 - Prenatal air pollution exposure to diesel exhaust induces cardiometabolic disorders in adulthood in a sex-specific manner
AU - Rousseau-Ralliard, Delphine
AU - Richard, Christophe
AU - Hoarau, Pauline
AU - Lallemand, Marie-Sylvie
AU - Morillon, Lucie
AU - Aubrière, Marie-Christine
AU - Valentino, Sarah A
AU - Dahirel, Michèle
AU - Guinot, Marine
AU - Fournier, Natalie
AU - Morin, Gwendoline
AU - Mourier, Eve
AU - Camous, Sylvaine
AU - Slama, Rémy
AU - Cassee, Flemming R
AU - Couturier-Tarrade, Anne
AU - Chavatte-Palmer, Pascale
N1 - Funding Information:
This work was supported by the French National Research Agency [ ANR-13-CESA-0011 EPAPP , 2012, scientific coordinator: Pascale Chavatte-Palmer] and European Union [ERC consolidator 311765 E-DOHaD , 2012, scientific coordinator: Rémy Slama].
Publisher Copyright:
© 2021 The Authors
PY - 2021/9/1
Y1 - 2021/9/1
N2 - BACKGROUND: 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.OBJECTIVES: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: In utero exposure to air pollution predisposed rabbit offspring to cardiometabolic disorders in a sex-specific manner.
AB - BACKGROUND: 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.OBJECTIVES: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: In utero exposure to air pollution predisposed rabbit offspring to cardiometabolic disorders in a sex-specific manner.
KW - Adult offspring
KW - Fetal programming
KW - Gestational exposure
KW - Intergenerational effect
KW - Rabbit biomedical model
UR - http://www.scopus.com/inward/record.url?scp=85111548465&partnerID=8YFLogxK
U2 - 10.1016/j.envres.2021.111690
DO - 10.1016/j.envres.2021.111690
M3 - Article
C2 - 34273365
SN - 0013-9351
VL - 200
SP - 1
EP - 13
JO - Environmental Research
JF - Environmental Research
M1 - 111690
ER -
