Effects of Maternal Exposure to Di-(2-ethylhexyl) Phthalate during Fetal and/or Neonatal Periods on Atopic Dermatitis in Male Offspring

BACKGROUND Di-(2-ethylhexyl) phthalate (DEHP) has been widely used in polyvinyl chloride products and is ubiquitous in developed countries. Although maternal exposure to DEHP during fetal and/or neonatal periods reportedly affects reproductive and developmental systems, its effects on allergic diseases in offspring remain to be determined. OBJECTIVES In the present study, we examined whether maternal exposure to DEHP during fetal and/or neonatal periods in NC/Nga mice affects atopic dermatitis-like skin lesions related to mite allergen in offspring. METHODS We administered DEHP at a dose of 0, 0.8, 4, 20, or 100 microg/animal/week by intraperitoneal injection into dams during pregnancy (gestation days 0, 7, and 14) and/or lactation (postnatal days 1, 8, and 15). Eight-week-old male offspring of these treated females were injected intradermally with mite allergen into their right ears. We then evaluated clinical scores, ear thickening, histologic findings, and protein expression of eotaxin in the ear. RESULTS Maternal exposure to a 100-microg dose of DEHP during neonatal periods, but not during fetal periods, enhanced atopic dermatitis-like skin lesions related to mite allergen in males. The results were concomitant with the enhancement of eosinophilic inflammation, mast cell degranulation, and protein expression of eotaxin in overall trend. CONCLUSION Maternal exposure to DEHP during neonatal periods can accelerate atopic dermatitis-like skin lesions related to mite allergen in male offspring, possibly via T helper 2 (T(H)2)-dominant responses, which can be responsible, at least in part, for the recent increase in atopic dermatitis.