Exposure to di(2-ethylhexyl) phthalate and diisononyl phthalate during adulthood disrupts hormones and ovarian folliculogenesis throughout the prime reproductive life of the mouse

Abstract

Di(2-ethylhexyl) phthalate (DEHP) is a phthalate commonly used for its plasticizing capabilities. Because of the wide production and use of DEHP, humans are exposed to DEHP on a daily basis. Diisononyl phthalate (DiNP) is often used as a DEHP replacement chemical, and because of the increased use of DiNP, humans are increasingly exposed to DiNP over time. Of concern is that DEHP and DiNP both exhibit endocrine disrupting capabilities, and little is known about how short-term exposure to either of these phthalates affects aspects of female reproduction. Thus, this study tested the hypothesis that short-term exposure to DEHP or DiNP during adulthood has long-lasting consequences on ovarian follicles and hormones in female mice. Female CD-1 mice aged 39–40 days were orally dosed with either vehicle control (corn oil), DEHP (20 μg/kg/day–200 mg/kg/day), or DiNP (20 μg/kg/day–200 mg/kg/day) for 10 days. Ovarian follicle populations, estradiol, testosterone, progesterone, follicle stimulating hormone (FSH), and inhibin B were analyzed at time points immediately post-dosing and 3, 6, and 9 months post-dosing. The results indicate that 10 days of exposure to DEHP and DiNP changed the distribution of ovarian follicle populations and sex steroid hormones at multiple time points, including the last time point, 9 months post-dosing. Further, FSH was increased at multiple doses up to 6 months post-dosing. Inhibin B was not affected by treatment. These data show that short-term exposure to either DEHP or DiNP has long-term consequences that persist long after cessation of exposure.