Effects of Maternal Hyperthermia on the Palatal Mesenchyme Development of Hsp70 Knock-out Mice Fetuses

Oh, Jung Keun; Kim, Won Kyu

Abstract

To investigate the effects of maternal hyperthermia on the development of the palate, pregnant Hsp70 knock-out mice at gestational day (GD) 8.5 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 WT mice fetuses were used as the control group. Fetuses were collected at embryonic day 13.5, 14.5 and 15.5 (E13.5, E14, 5 and E15.5). Heads followed by removal of the mandible and the tongue were obtained and photographed for palatal development. Developing palates were processed for histological and immunohistochemical studies. Tissue sections were immunostained for TGF-beta2, FGF-8 and fibronectin, and observed with light microscope. The obtained results were as follows: Cleft palate was formed in heat-treated Hsp70 KO fetuses at E14.5 and E15.5. Immunohistochemical findings indicated that TGF-beta2 expression of the experimental fetuses were more delayed than that of the control fetuses. Mesenchyme under the medial edge epithelium (MEE) and cells of MEE showed continuously strong positive TGF-beta2 reactivity at E15.5. FGF-8 was revealed in both of the mesenchyme and the epithelium at the same time. FGF-8 immunoreactivity in the mesenchyme and the epithelium of the heat-treated fetuses showed strong reactivity at E15.5. In the experimental fetuses fibronectin was revealed the mesenchyma and basal lamina at E15.5. Taken together, it is suggested that maternal hyperthermia induces continuous expression of TGF-beta2 and FGF-8 in the mesenchyme and delayed expression of fibronectin. These should affect the normal palatogenesis and result in cleft palate.