title: Maternal exposure to diluted diesel engine exhaust alters placental function and induces intergenerational effects in rabbits.
abstract: Airborne pollution is a rising concern in urban areas. Epidemiological studies in humans and animal experiments using rodent models indicate that gestational exposure to airborne pollution, in particular diesel engine exhaust (DE), reduces birth weight, but effects depend on exposure duration, gestational window and nanoparticle (NP) concentration. Our aim was to evaluate the effects of gestational exposure to diluted DE on feto-placental development in a rabbit model. Pregnant females were exposed to diluted (1 mg/m(3)), filtered DE (NP diameter ≈ 69 nm) or clean air (controls) for 2 h/day, 5 days/week by nose-only exposure (total exposure: 20 days in a 31-day gestation).
  
  
  
  DE exposure induced early signs of growth retardation at mid gestation with decreased head length (p = 0.04) and umbilical pulse (p = 0.018). Near term, fetal head length (p = 0.029) and plasma insulin and IGF1 concentrations (p = 0.05 and p = 0.019) were reduced. Placental function was also affected, with reduced placental efficiency (fetal/placental weight) (p = 0.049), decreased placental blood flow (p = 0.009) and fetal vessel volume (p = 0.002). Non-aggregated and "fingerprint" NP were observed at various locations, in maternal blood space, in trophoblastic cells and in the fetal blood, demonstrating transplacental transfer. Adult female offspring were bred with control males. Although fetoplacental biometry was not affected near term, second generation fetal metabolism was modified by grand-dam exposure with decreased plasma cholesterol (p = 0.008) and increased triglyceride concentrations (p = 0.015).
  
  
  
  Repeated daily gestational exposure to DE at levels close to urban pollution can affect feto-placental development in the first and second generation.
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy en Josas, France.|PremUp Foundation, Paris, France.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Valentino
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy en Josas, France.|PremUp Foundation, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Tarrade
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy en Josas, France.|PremUp Foundation, Paris, France.
authors.forename: Josiane
authors.initials: J
authors.lastname: Aioun
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy en Josas, France.|PremUp Foundation, Paris, France.
authors.forename: Eve
authors.initials: E
authors.lastname: Mourier
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy en Josas, France.|PremUp Foundation, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Richard
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy en Josas, France.|PremUp Foundation, Paris, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Dahirel
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy en Josas, France.|PremUp Foundation, Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Rousseau-Ralliard
authors.affiliation: UFR de Pharmacie, Univ Paris-Sud, EA 4041/4529 Lip (Sys), Châtenay-Malabry, France.|Hôpital Européen Georges Pompidou (AP-HP), Laboratoire de Biochimie, UF Cardio-Vasculaire, Paris, France.
authors.forename: Natalie
authors.initials: N
authors.lastname: Fournier
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy en Josas, France.|PremUp Foundation, Paris, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Aubrière
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy en Josas, France.|PremUp Foundation, Paris, France.
authors.forename: Marie-Sylvie
authors.initials: MS
authors.lastname: Lallemand
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy en Josas, France.|PremUp Foundation, Paris, France.
authors.forename: Sylvaine
authors.initials: S
authors.lastname: Camous
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy en Josas, France.|PremUp Foundation, Paris, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Guinot
authors.affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, Jouy en Josas, France.
authors.forename: Madia
authors.initials: M
authors.lastname: Charlier
authors.affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, Jouy en Josas, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Aujean
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy en Josas, France.|PremUp Foundation, Paris, France.
authors.forename: Hala
authors.initials: H
authors.lastname: Al Adhami
authors.affiliation: Centre for Sustainability, Environment and Health, National Institute for Public Health and the Environment, Bilthoven, Netherlands.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Fokkens
authors.affiliation: Inserm and Univ. Grenoble Alpes, U823, IAB Research Center, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Grenoble, France.
authors.forename: Lydiane
authors.initials: L
authors.lastname: Agier
authors.affiliation: Centre for Sustainability, Environment and Health, National Institute for Public Health and the Environment, Bilthoven, Netherlands.
authors.forename: John A
authors.initials: JA
authors.lastname: Boere
authors.affiliation: Centre for Sustainability, Environment and Health, National Institute for Public Health and the Environment, Bilthoven, Netherlands.|Institute of Risk Assessment Sciences, Utrecht University, Utrecht, Netherlands.
authors.forename: Flemming R
authors.initials: FR
authors.lastname: Cassee
authors.affiliation: Inserm and Univ. Grenoble Alpes, U823, IAB Research Center, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Grenoble, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Slama
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy en Josas, France. pascale.chavatte@jouy.inra.fr.|PremUp Foundation, Paris, France. pascale.chavatte@jouy.inra.fr.
authors.forename: Pascale
authors.initials: P
authors.lastname: Chavatte-Palmer
mesh_terms: D000818:Animals; D005260:Female; D018811:Maternal Exposure; D010920:Placenta / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011817:Rabbits; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D001335:Vehicle Emissions