In utero exposure to diesel exhaust and its effect on placental transcriptional response in rabbit F2 generation

ABSTRACT: Atmospheric pollution is a rising concern in urban areas and a major contributor to people’s mortality, with potential intergenerational consequences. Our aim was to evaluate the effects of exposure of pregnant F0 females to diluted diesel exhaust (DE) on feto-placental development in the second generation (F2). These rabbits were exposed to diluted and filtered DE (E: exposed group) or clean air (C: Control group) for 2h/day, 5days/week by nose-only exposure from 3rd to 27th days post-conception (dpc). Not exposed anymore after birth, female offspring (F1) were mated with control males at adulthood. F2 feto-placental units were collected at 28dpc. Fatty acid profiles were determined from fetal and maternal plasma, maternal liver and placenta by gas chromatography. Placental structure was explored by stereology while placental gene expression was analyzed using a dedicated microarray. At 28dpc, maternal F1 biochemistry was not different between groups, although F1 E females exhibited increased content of hepatic neutral lipid. Similarly the content of lipid was higher in F2 E placentas, mostly by monounsaturated fatty acids while arachidonic acid was reduced. The proportion of n-3 polyunsaturated fatty acids (n-3 PUFA) was increased whereas AA decreased in F2 E fetal plasma compared to Controls. No structural change was observed in placentas between groups. GSEA analysis of transcriptomic data revealed that gene involved in proteasome complex and ubiquitin pathways were up-regulated in E placentas when compared to C placentas, whereas those involved in ion channel or inflammation regulations were down-regulated. In conclusion, in utero exposure of F1 females to DE can affect both placental function and fetal metabolism in the second generation (F2). Placental FA profiles suggest adaptive protective mechanisms against inflammation, through placental storage of non-essential FA and the favored transplacental transfer of n-3 PUFA. The fetal physiological consequences of observed alterations in placental genes involved in protein metabolism and intracellular signaling remain to be determined. In order to evaluate the intergenerational effects to the F2 generation of in utero F1 exposure to DE, we chose the rabbit model because of its hemochorial placenta closer to the human one (Fischer et al 2012; Furukawa, 2014) than those of rodents. The present study follows our recent publication related to the effects of diesel exhaust exposure of rabbit female F0 during gestation on feto-placental development in F1 and F2 generations (Valentino et al., 2016) where we have shown that F2 feto-placental biometry was not disturbed consecutively to the in utero exposure of the F1 generation (Valentino et al., 2016). Nevertheless, these macroscopically normal fetuses had reduced plasma total cholesterol (-25.9%) and non-HDL cholesterol (-26%) associated with an increase in plasma triglycerides concentrations (+25.9%) compared to F2 control group (Valentino et al., 2016). In the present study, placental function in the second generation was explored at a biochemical and molecular levels in order to understand how the placenta contributed to the fetal dyslipidemia without affecting the biometry.

ORGANISM(S): Oryctolagus cuniculus

PROVIDER: GSE109831 | GEO | 2019/07/25

REPOSITORIES: GEO