Gestational di(2-ethylhexyl) phthalate alters pregnancy outcomes, growth, biochemical, hematological, and reproductive hormone profiles in male offspring mice

Abstract

Due to its versatile use, di(2-ethylhexyl) phthalate (DEHP) is omnipresent in the environment and has become a significant health concern. Gestational exposure to contaminants may disrupt fetal intrauterine development and, in the long term, affect the postnatal stage. The present study aimed to investigate the effects of human-equivalent doses of DEHP on pregnancy outcomes, growth, biochemical, hematological, and hormone profiles in male offspring mice. Pregnant Swiss albino female mice were divided into different groups (T0- control group received filtered water; T1- 2 mg DEHP/kg body weight (BW)/day; T2- 4 mg DEHP/kg BW/day; and T3- 6 mg DEHP/kg BW/day) and treated throughout gestation. After the treatment period, pregnancy outcomes, postnatal body growth, hematological & biochemical parameters, organ development, and hormone profiles were evaluated in male offspring mice. Lower doses resulted in prolonged gestation, fewer pups, higher birth weights, and a more favorable sex ratio towards males. Serum cholesterol, triglycerides, and liver enzymes increased, especially at lower doses. Total leukocyte and circulating eosinophil counts were remarkably decreased in all treatment group offspring, but more prominently in the lower dose. Conversely, RBC and platelet counts were significantly increased. Thus, the more significant alterations in different parameters at lower doses indicate a non-monotonic dose-response pattern, in which the chemical\'s effect does not steadily increase with dose; sometimes a low dose exerts a greater or different impact than a high dose. Gestational exposure to DEHP significantly affects pregnancy outcomes, postnatal growth and development, and the biochemical profile of male mouse offspring in a non-monotonic dose-response pattern.