Developmental exposure to di(2-ethylhexyl) phthalate impairs endocrine pancreas and leads to long-term adverse effects on glucose homeostasis in the rat

Abstract

—Di(2-ethylhexyl) phthalate (DEHP), a typical endocrine-disrupting chemical (EDC), is widely used as plasticizer. DEHP exposure in humans is virtually ubiquitous, and those undergoing certain medical procedures can be especially high. In this study, we investigated whether developmental DEHP exposure disrupted glucose homeostasis in the rat and whether this was associated with the early impairment in endocrine pancreas. Pregnant Wistar rats were administered DEHP (1.25 and 6.25 mg·kg−1·day−1) or corn oil throughout gestation and lactation by oral gavage. Body weight, glucose and insulin tolerance, and β-cell morphometry and function were examined in offspring during the growth. In this study, developmental DEHP exposure led to abnormal β-cell ultrastructure, reduced β-cell mass, and pancreatic insulin content as well as alterations in the expression of genes involved in pancreas development and β-cell function in offspring at weaning. At adulthood, female DEHP-exposed offspring exhibited elevated blood glucose, reduced serum insulin, impaired glucose tolerance, and insulin secretion. Male DEHP-exposed offspring had increased serum insulin, although there were no significant differences in blood glucose at fasting and during glucose tolerance test. In addition, both male and female DEHP-exposed offspring had significantly lower birth weight and maintained relatively lower body weight up to 27 wk of age. These results suggest that developmental exposure to DEHP gives rise to β-cell dysfunction and the whole body glucometabolic abnormalities in the rat. DEHP exposure in critical periods of development can be a potential risk factor, at least in part, for developing diabetes.