Maternal Exposure To Phthalate Drives Skin Changes Associated With Increased Susceptibility To House Dust Mite Induced Atopic Dermatitis In Offspring

Epidemiologic studies indicate a link between maternal phthalate exposure and the development of Atopic Dermatitis (AD). Higher Trans-Epidermal Water Loss (TEWL) indicating skin barrier dysfunction, and cutaneous inflammation are hallmarks of AD. However, there is a little mechanistic information regarding the connection between maternal phthalate exposure offspring AD development. To model maternal exposure, dams were intraperitonially injected with di-2-ethylhexyl phthalate (DEHP; 0.1mg/ 0.1mL) or saline from shortly after delivery until 3-days prior to weaning. Within 1 week of weaning, pups were exposed to cutaneous allergen (house dust mite; HDM)). PBS or HDM-soaked bandages were affixed to the skin for a week using tagaderm. TEWL measurements were made at baseline (prior to any patching), or 1, 3, 5 and 7 days after patch removal. 7 days after patch removal, skin was re-shaved, and patched again for up to 4 cycles. Four groups of mice were generated: DEHP-exposed and HDM-treated (DEHP-HDM), DEHP-saline, saline-HDM, and saline-saline. TEWL values prior to any allergen exposure were not significantly different in offspring of PBS or DEHP dames. However, when exposed to HDM, DEHP mice showed significantly higher (p < 0.001) TEWL compared to DEHP-saline mice or saline-saline controls. Our data suggest that maternal exposure to phthalate alone does not alter the skin barrier function but changes the immune function of the offspring in a way that leads to enhanced susceptibility to allergen induced skin diseases. Additional analyses are underway to further elucidate the changes in the blood and skin transcriptome induced by maternal exposure to phthalates.