Prenatal Exposure to Persistent Organic Pollutants and Maternal Folic Acid Supplementation: Their Impact on Glucose Homeostasis in Male Rat Descendants
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abstract
Exposure to persistent organic pollutants (POPs) is associated with insulin resistance while folic acid (FA) may offer a protective effect. However, the paternal contribution to metabolic phenotypes in offspring is not well known yet. Hence, we investigated whether maternal exposure to POPs affects glucose homeostasis and whether maternal FA supplementation counteracts POP effects transmitted via male descendants. SpragueDawley founder dams (F0) were fed a diet containing 2 or 6 mg/kg of FA and were force-fed with either a POP mixture or corn oil for 9 weeks. Subsequent male descendants did not receive any treatment. Blood glucose, plasma insulin and C-peptide were measured during an oral glucose tolerance test in males aged 90 and 180 days from generation 1 (F1), 2 (F2) and 3 (F3). Prenatal POP exposure increased fasting glucose in 90-day-old F1 males and C-peptide in 90-day-old F2 males. Prenatal FA supplementation decreased C-peptide in 90 and 180-day-old F1 males. In 180-day-old F3 males, FA supplementation counteracted POPs on fasting and postglucose C-peptide, indicating reduced insulin secretion. Prenatal exposure to an environmentally relevant POP mixture caused abnormalities in glucose homeostasis that are transmitted from one generation to the next through the paternal lineage. Prenatal FA supplementation counteracted some of the deleterious effects of POPs on glucose homeostasis.
