Effects of Maternal Exposure to Di-(2-ethylhexyl) Phthalate during Fetal and/or Neonatal Periods on Atopic Dermatitis in Male Offspring Rie Yanagisawa,1 Hirohisa Takano,1 Ken-ichiro Inoue,1 Eiko Koike,1 Kaori Sadakane,2 and Takamichi Ichinose2 1Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Japan; 2Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita, Japan Abstract 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 µg/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-µg 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 (TH2) -dominant responses, which can be responsible, at least in part, for the recent increase in atopic dermatitis. Key words: atopic dermatitis, di-(2-ethylhexyl) phthalate, eosinophils, eotaxin, mast cells. Environ Health Perspect 116:1136–1141 (2008) . doi:10.1289/ehp.11191 available via http://dx.doi.org/ [Online 9 April 2008] Address to correspondence H. Takano, Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, 305-8506, Japan. Telephone: 81-29-850-2336. Fax: 81-29-850-2334. E-mail: htakano@nies.go.jp yanagi@nies.go.jp. Supplemental Material is available online at http://www.ehponline.org/members/2008/11191/suppl.pdf We thank M. Sakurai and N. Ueki for their technical assistance. The authors declare they have no competing financial interests. Received 18 December 2007 ; accepted 8 April 2008. The full version of this article is available for free in HTML or PDF formats. |