(114) The Effects of a Combination of  Western Diet and Phthalate Exposure on Gene Expression Levels in the Ovary

Stav Kramer¹, Zach Bomstein², Ashley Deviney¹, Mary J. Laws¹, Kimberly Allred², Clinton Allred², Arul Jayaraman³, Kyongbum Lee⁴, Jodi A. Flaws¹

¹Department of Comparative Biosciences, University of Illinois at Urbana Champaign, Urbana, IL; ²University of North Carolina Greensboro; ^3­­Texas A&M University, College Station, TX; ⁴Tufts University, Medford, MA

Abstract Text:

Phthalates are a diverse group of chemicals commonly used in a wide range of products, including food packaging, children's toys, and plastic containers. These compounds have been shown to negatively impact female reproductive health, but their effects in conjunction with a western diet—characterized by high fat and processed foods prevalent in the United States—are not well understood. This study investigates how the combined exposures to a western diet and phthalates affect processes in the ovary, with a focus on immune, steroidogenesis, and aryl hydrocarbon receptor gene expression (Il-1α, Il-1β, Il-1r1, Il1r2, Il-4, Il-6, Il-10, Tnf-α, 17β-Hsd, 3β-Hsd, Cyp17a1, Cyp11a1, Esr1, Esr2, and AhR). To do so, female C57BL/6 mice were divided into six experimental groups: vehicle diet, vehicle diet with di(2-ethylhexyl) phthalate (DEHP), vehicle diet with diisononyl phthalate (DiNP), western diet, western diet with DEHP, and western diet with DiNP. RNA was extracted from the ovaries of these mice to measure the expression levels of specific genes. The results indicate that DiNP exposure significantly increased Il-1β and Cyp17a1 expression in the ovary, irrespective of whether the mice were on a control or western diet. Furthermore, DiNP exposure significantly decreased Il-1r2 and 3β-Hsd expression in the ovary in mice on a control diet and mice on a western diet. In the DEHP group, western diet exposure significantly decreased expression of Cyp11a1 and 3β-Hsd.  In contrast, control diet with DEHP, control diet with DiNP, western diet with vehicle, western diet with DEHP, and western diet with DiNP did not significantly affect the expression of Il-1α, Il-1r1, Il-4, Il-6, Il-10, Tnf-α, 17β-Hsd, Esr1, Esr2, and AhR compared to control diet with vehicle. Overall, these findings indicate that DiNP and western diet exposure alter the expression of some inflammatory and steroidogenic markers in the mouse ovary. Supported by NIH  R01 ES034112.