Maternal Di-(2-Ethylhexyl) Phthalate (DEHP) Exposure Impairs Insulin Signal in the Liver and Gastrocnemius Muscles of Female Offspring Rats

Abstract

Di-(2-Ethylhexyl) Phthalate (DEHP) is a potent endocrine disruptor that is commonly present in consumer products and cosmetics. Exposure to DEHP during gestational and lactational periods can adversely affect glucoregulation and lead to the onset of diabetes in progeny. The liver and gastrocnemius muscles play an important role in regulating glucose metabolism and insulin action. This study was designed to investigate the effect of maternal DEHP exposure on insulin signaling molecules in the liver and gastrocnemius muscles of adult female offspring rats. Rat dams were given DEHP (10 and 100 mg/kg b.wt./day) by oral gavage from gestation day 9 (GD 9) to the end of the lactation period Postnatal Day (PND) 21. On PND 80, female offspring rats in diestrus were euthanized and found reduced body weight, organ (liver and gastrocnemius) weight, and hyperglycemia in DEHP-exposed rats. Western blots revealed a dose-dependent reduction in the expression of Insulin Receptor - (IR), IRS, Akt, and GSK-3β proteins as well as their phosphorylated forms in the liver and gastrocnemius muscles of DEHP-exposed offspring rats. Maternal DEHP exposure reduced the levels of GLUT2 and GLUT4 level in the liver and gastrocnemius muscles, respectively. Liver and renal function markers were dose-dependently increased in the serum of offspring female rats born to DEHP exposed mother during gestation and lactation. Thus, the study revealed that maternal DEHP exposure impaired the expression of insulin signaling molecules in the two important tissues involved in glucose metabolism, the liver and gastrocnemius muscles, suggesting that phthalates exposure during development may contribute to the onset of diabetes in female offspring.