A Systematic Review on the Effects of Maternal Di-2-Ethylhexyl Phthalate (DEHP) Exposure and its Role in the Development of Insulin Resistance and Metabolic Syndrome in Offsprings

Phthalates are synthetic compounds wildly used as plasticizers and di-(2-ethylhexyl) phthalate (DEHP) is one such phthalate, commonly used in numerous polyvinyl chloride (PVC) products. DEHP gets leached from PVC and ultimately ends up in biological systems of humans and animals. Phthalates are able to cross the placenta leading to its exposure during critical windows of foetal development. The present review focuses on effect of maternal DHEP exposure in offsprings and its role in development of insulin resistance and metabolic syndrome during adulthood in rodent models. The effect of maternal DEHP exposure in liver of the offsprings (f1) reduces insulin receptor (InsR), IRS1, Akt, resulting in defective PI3K-Akt insulin signalling. In pancreatic islets, maternal DEHP exposure brings about suppression of certain transcription factors involved in insulin synthesis and also glucokinase reducing insulin biosynthesis. Concurrently, in adipose tissue, prenatal and perinatal DEHP exposure brings about altered adipocyte development, induction of hypertrophy of the cell, upregulation of genes involved in adipogenesis and lipid metabolism. In summary, pre and postnatal DEHP exposure interferes with the insulin metabolism and glucose homeostasis along with lipid metabolism in liver, pancreas and adipose tissue in offsprings. This includes epigenetic modifications of genes related to insulin synthesis, uptake and utilization of glucose, lipid metabolism resulting in glucose intolerance, dyslipidemia and insulin resistance, ultimately leading to metabolic syndrome during early adulthood.