| Summary: | Persistent organic pollutants (POPs) are toxic compounds, highly resistant to degradation which are transported by atmospheric and ocean currents up to the Arctic. As a result, Inuit people are directly exposed to POPs through the contamination of the Arctic food chain. On the other hand, the prevalence of type-2 diabetes (T2D) has dramatically increased in this population during the last decades. In addition, prenatal exposure to POPs is associated with the onset of metabolic disorders in offspring later life. As a methyl group donor, folic acid (FA) may limit the deleterious effects of POPs. The general objective of this thesis is to determine whether FA supplementation of dams’ diet before and during pregnancy can overcome the effects of prenatal exposure to POPs, on glucose homeostasis, lipid response and inflammatory response in three generations of male descendants via paternal transmission in a rat model. To achieve our objectives, we reproduced a prenatal paternal exposure, using a three-generation rat model. Sprague-Dawley females (F0) were exposed to a POPs mixture (or corn oil), +/- FA supplementation through the diet before and during gestation for a total of nine weeks. F1 and F2 males were mated with untreated females. In F1 males, prenatal POPs exposure increased fasting glucose and C-peptide levels, which is a biomarker of insulin secretion, as well as hepatic triglyceride and plasma and hepatic cholesterol levels. F2 males from the POPs-treated lineage also showed higher plasma Cpeptide levels. Prenatal FA supplementation lowered plasma C-peptide and plasma cholesterol levels in F1 males. In F3 males, FA supplementation counteracted the POPsinduced higher C-peptide levels indicating normalization of insulin secretion. No differences in the inflammatory response of F1, F2 and F3 males were observed following POPs exposure or FA supplementation. In conclusion, our work shows that prenatal POPs exposure can lead to the onset of cardiometabolic disorders up to the F3 generation of male rats via ...
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