Maternal Exposure to an Environmentally Relevant Phthalate Mixture Modulates the Steroidogenic Genes in the Adrenal Glands Throughout Postnatal Development of Male Rats

Abstract

Phthalates are a group of chemicals used as plasticizers to enhance the malleability and flexibility of various products. The adrenal glands are responsible for producing hormones that maintain homeostasis, regulate blood pressure, and mediate stress responses. Early exposure of the adrenal glands to environmental toxicants can impair important responses, which can result in damage of adrenal development and functionality. This study aimed to investigate the effects of maternal exposure to a phthalate mixture on the development of the offspring's adrenal glands. Pregnant females (SD) were divided into three groups and treated daily, orally, from gestational day (GD) 10 to postnatal day (PND) 21 with corn oil (vehicle; Control: C) or a phthalate mixture containing 21% DEHP, 35% DEP, 15% DBP, 8% DiBP, 5% BBzP and 15% DiNP at doses of 20 μg/kg/day (T1) or 200 mg/kg/day (T2). The pups were weighed and euthanized at PND22, PND120, and PND540. Adrenal glands were collected and analyzed for steroidogenesis. Our results indicate that both doses of the mixture affected cholesterol metabolism and its mitochondrial internalization, altered the expression of StAR, Cyp11a1, and Cyp19a1, and created a microenvironment conducive to estrogenization. With aging, both doses modulated steroidogenic genes, leading to indications of hyposecretion. The higher dose (T2) also induced mitochondrial stress through the overexpression of Gpx1. In conclusion, our findings highlight the genic expression alterations in the adrenal glands of offspring exposed to phthalates during gestation and lactation, as well as their long-term consequences across different developmental stages, as potential impacts on adrenal homeostasis and metabolic functions.