The Effects of Hyperthermia on FGF-8 and BMP-4 Expression during Early Odontogenesis in Hsp70 Knock-out Mice Fetuses

Ahn, Dong Choon; Kim, Jong Ryong; Kim, Won Kyu

Abstract

During early tooth development, multiple signaling molecules are expressed in the dental lamina and induce the dental mesenchyme. One signal, FGF-8, is expressed in the early dental epithelium, another one, BMP-4, has been shown to induce morphologic changes in dental mesenchyme. Meanwhile, hyperthermic exposure during pregnancy, as one of teratogens, is known to disturbe normal development and induce several congenital anomalies. This study is aimed to investigate the effects of maternal hyperthermia on the expressions of FGF-8 and BMP-4 in early odontogenesis. The pregnant Hsp70 knock-out at gestational day 8 were immersed in 43degrees C water bath until their body core temperature reached at 43degrees C. Thereafter, pregnant mice were given more 5 minutes hyperthermic exposure. Heat-untreated Hsp70 KO mice fetuses were used as the control group. Fetuses were collected at embryonic day (ED) 13, 15 and 17. Developing tooth in the mandible was processed for immunohistochemical study. Tissue sections were immunostained for FGF-8 and BMP-4 and observed with light microscope. The obtained results were as follows: Tooth development in the heat shocked (HS) group is delayed rather than the control group in the given developmental period. FGF-8 immunolocalization in control group at ED 13 was gradually decreased compared to the HS group which showed continuously positive immunoreaction. BMP-4 immunolocalization was detected in dental mesenchyme, however, there was no positive immunoreaction found in HS group. These results suggest that maternal hyperthermia should induce the early odontogenesis, delay the expression of FGF-8 in dental epithelium, and disturbe the expression of BMP-4 in dental mesenchyme. Consequently, hyperthermic exposure during pregnancy affects epithelial-mesenchymal interactions.