フタル酸エステルによる妊娠子宮での細胞増殖阻害

抄録

Di(2-ethylhexyl)phthalate (DEHP) is a manufactured chemical widely used for plastics to make them flexible. It is present in many plastics, especially in vinyl materials. DEHP non-covalently binds to plastics, therefore is will leach out of the products. Exposure to DEHP during pregnancy has been known to cause developmental defect of embryos. Although this toxic effect of DEHP to embryos are believed to be a consequence of direct actions of DEHP in embryos, possible contribution of indirect mechanism through its toxic effect to the maternal body still remains and to be clarified. Therefore, we here examined the effect of DEHP to maternal uterus. ICR female mice were administered DEHP for 7 days from the day which a vaginal plug was found. The uterus was analyzed at gestational day 17, 2 days before in due date. Gene expression analyses by quantitative RT-PCR indicated the increase in expression of Fabp4, a multivalent secreted protein affecting inflammation and/or cell proliferation. The expression of Ki67 and Pcna mRNAs were lower in the DEHP-treated uterus, suggesting that the DEHP intake suppresses cell proliferation in the uterus of due date imminentness. Because Fabp4 has been implicated to inhibit the cell proliferation through the regulation of uncoupling protein 2 (Ucp2), we examined the expression of Ucp2 mRNA and found the decreased expression of Ucp2 in the DEHP-administered uterus. These results indicate that intake of DEHP in the early pregnant stages affects cell proliferation in the parturient uterus through the regulation of Ucp2.