Programming of intestinal homeostasis in male rat offspring after maternal exposure to chlorpyrifos and/or to a high fat diet

Abstract

Alteration of programming of the intestinal wall maturation may be responsible for non-communicable chronic diseases in adulthood. It may originate from prenatal exposure of mothers to deleterious environmental factors such as pesticides or western diet. This work was undertaken to determine whether disturbances of the digestive tract function and of innate immunity of offspring at adulthood could be due to maternal exposure to a pesticide, chlorpyrifos (CPF) and a High Fat Diet (HFD) starting 4 months before gestation and lasting until weaning of offspring. Fifty-one male Wistar rats coming from 4 groups of dams exposed to CPF, HFD, both and control were followed from birth to 8 weeks of age. They were fed standard chow and received no treatment. The maternal pesticide exposure slows down fetal and postnatal weight gain without histological injuries of the gut mucosa. CPF or HFD both induced modifications of tight junctions and mucins genes expressions without inducing an increase in epithelial permeability or an inflammatory state. Co-exposure to both CPF and HFD did not exacerbate the effects observed with each factor separately. Despite the lack of direct contact except through breast milk until weaning, CPF or HFD maternal exposure have demonstrated preliminary gut barrier impacts on offspring.

Perinatal and post-weaning exposure to a high-fat diet causes histomorphometric, neuroplastic, and histopathological changes in the rat ileum

“…Guiburdenche et al 2021, in their study, showed that offspring of mothers exposed to HFD showed a reduction in the expression of Muc 2 in the ileum, which may explain the inflammation observed in these animals. 57 The ileitis found in this study is related to the increase in the proportion of IELs and histopathological findings. Along with enterocytes, Paneth cells and goblet cells, IELs actively participate in the protection of the epithelial barrier through the secretion of TGF-β, 58 but they can also contribute to inflammation with the secretion of pro-inflammatory cytokines and AMPs regulated by commensal bacteria.…”

Impact of Pesticide Residues on the Gut-Microbiota–Blood–Brain Barrier Axis: A Narrative Review

“…Because the exposure to pesticides is often accompanied with saturated fats and refined sugars (an unbalanced diet based on fast food and processed food), other studies assessed the impact of the association of CPF to a High Fat Diet (HFD) on intestinal microbiota and the IB. Guibourdenche and colleagues confirmed that the chronic perinatal exposure to the NOAEL dose of CPF alone induced a decrease in transcriptional TJs expression and also demonstrated an increase in proinflammatory cytokines and is aggravated by the association to an HFD [ 31 , 122 ].…”

“…Dysbiosis is defined as an imbalance in the GM and/or its functions due to the loss of beneficial microbes and the increase in pathogenic ones that might induce inflammation and immune dysregulation leading to an unhealthy outcome [ 27 , 28 , 29 ]. As a result, the alteration in bacterial metabolites modulates the IB permeability and thus generates an uncontrolled and permissive passage of not only proinflammatory agents (cytokines, interleukins, bacteria, and bacterial products) [ 30 , 31 ] but also bacterial neurotransmitters from the microbial environment and immune cells that can compromise intestinal and brain homeostasis by affecting the BBB integrity leading to inflammatory and neurological disorders [ 32 , 33 ]. The passage of viable bacteria of the gastrointestinal flora is through the barrier of the intestinal mucosa (the lamina propria) to the mesenteric nodes and then to normally sterile internal organs and is defined as “bacterial translocation” [ 26 ].…”

Endocrine disrupting chemicals and male fertility: from physiological to molecular effects

“…The maternal exposure to CPF had a negative impact on intestinal homeostasis of 51 male rats of the offspring (Wistar rats). Therefore, despite the lack of direct contact with pesticides except through breast milk until weaning, maternal exposure to the pesticide appeared to delay fetal and postnatal weight gain ( 45 , 46 ). In addition to all of these effects, CPF is currently considered an EDC ( 47 ).…”