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.

First Year Growth in Relation to Prenatal Exposure to Endocrine Disruptors — A Dutch Prospective Cohort Study

“…Studies in sheep have shown that prenatal exposure to testosterone is associated with lower birth weight, developmental changes in insulin-like growth factor (IGF)/IGF binding protein system, and insulin resistance (reviewed in [50]). In a recent study in which rats were developmentally exposed to the suspected androgen DEHP, female rats were observed to have impaired glucose tolerance and insulin secretion [51]. Male rats showed increased serum insulin levels, and both female and male rats had a significantly lower birth weight than controls.…”

Mono-(2-Ethylhexyl) Phthalate Induces Injury in Human Umbilical Vein Endothelial Cells

“…As an endocrine disruptor, DEHP altered male sexual differentiation [7] and disturbed energy metabolism in animals [[8],[9]]. Investigations mainly focused on the potential adverse effects of DEHP and MEHP, its active metabolite, on the reproductive system, carcinogenicity, liver, kidney and developmental toxicities [10], [11].…”

Analysis of the in�vitro effects of di‑(2‑ethylhexyl) phthalate exposure on human uterine leiomyoma cells

“…Furthermore, DEHP is an endocrine disruptor that is able to alter sexual differentiation and energy metabolism (10)(11)(12). Given its chemical structure, DEHP easily enters food, air and even the human body.…”

“…Di-(2-ethylhexyl) phthalate (DEHP) is the most common environmental endocrine disruptor (10)(11)(12). DEHP is widely used in consumer products, including food packaging, medical devices and toys, to improve the flexibility and durability of polyvinyl chloride-based plastics.…”