12-O-tetradecanoyl-phorbol-13-acetate-induced rat embryo malformations in vitro are associated with an increased relative abundance of embryonic E-cadherin mRNA.
Epithelial-cadherin (E-cadherin) is a member of a family of Ca(2+)-dependent cell adhesion molecules which are localized in zonulae adherens and play an important role during development. E-cadherin is abundant in rat embryos and their yolk sacs during organogenesis. The phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), has been reported to disrupt the morphology and functional development of the rat embryonic visceral yolk sac. The present study investigated the possibility that the effect of TPA on yolk sac development may be due to the altered expression of E-cadherin. Rat embryos, with their yolk sacs intact, were cultured on day 10 of gestation for 1 hr. At this time the vehicle, dimethyl sulfoxide (DMSO), or TPA (at different concentrations) was added to the culture medium; the cultures were continued for up to 24 hr. Embryos and yolk sacs were collected separately at the end of each culture period. The relative abundances of E-cadherin mRNA and protein were analyzed with Northern and Western blot analyses. Despite the TPA-induced abnormalities in yolk sac development, the relative abundance of E-cadherin mRNA or protein in the yolk sac was not altered by TPA exposure. However, in embryos exposed to dysmorphogenic concentrations of TPA, the relative abundance of E-cadherin mRNA was significantly increased after 24 hr in culture, compared to either controls or embryos exposed to non-dysmorphogenic concentrations of TPA. The magnitude of the increase in embryonic E-cadherin mRNA appeared to correlate with the severity of the embryo malformations.(ABSTRACT TRUNCATED AT 250 WORDS)
Chen
B
B
Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada.
Hales
B F
BF
D000014:Abnormalities, Drug-Induced / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D015820:Cadherins / Q000235:genetics*; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000187:drug effects; D004789:Enzyme Activation; D011493:Protein Kinase C / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*; D015017:Yolk Sac / Q000187:drug effects / Q000378:metabolism
D015820:Cadherins; D012333:RNA, Messenger; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate