Abstract
There is growing evidence that organophosphate esters (OPEs) can act as endocrine-disrupting chemicals. However, only a few studies have assessed the effects of OPE exposure on one of the most important endocrine glands in the body, the adrenal gland. Our aim was to test the effects of a mixture of OPEs detected in Canadian house dust on adrenal function in Sprague Dawley rats. Adult male and female rats (n = 15 per treatment group) were administered either a vehicle or an OPE mixture (0.048, 1.6, or 48 mg/kg bw/d) for 70 to 72 d via their diet. With OPE exposure, adrenal glands from male adult rats were reduced in weight, whereas those of female rats showed an increase in weight. This led us to investigate whether OPEs induce sex-specific effects on adrenal gland function and the mechanisms involved. Serum levels of two adrenal hormones, aldosterone and corticosterone, were decreased only in male serum samples. Serum levels of renin and adrenocorticotropic hormone, which regulate aldosterone and corticosterone synthesis, respectively, were assessed. Exposure to the OPE mixture decreased renin levels only in males. Serum biochemistry analysis revealed that triglycerides and LDL cholesterol levels were increased in males. Transcriptomic analysis revealed that the top affected pathways in male adrenal glands from all three treatment groups were related to potassium channels, which play a role in regulating aldosterone and corticosterone levels. The most affected pathways in female adrenal glands were related to cholesterol biosynthesis and immune functions. These results show that an environmentally relevant mixture of OPEs affects adrenal function and that these effects are sex specific.