12-O-Tetradecanoyl-phorbol-13-acetate (TPA) induced congenital kidney defects and embryomortality in the CD-1 mouse.
CD-1 Mice were treated with daily intraperitoneal injections of 10 or 100 micrograms/kg 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on pregnancy days 8, 9 and 10 or 11, 12 and 13 (early and late organogenesis). By the same regimen, the LD50 for TPA was about 450 micrograms/kg. TPA treatment induced embryomortality, fetal malformation and reduced fetal weight, generally in a dose-related manner. TPA treatment (100 micrograms/kg) was markedly more embryolethal on days 11-15 (68%/litter) than in early organogenesis (18%/litter). Renal malformations were observed in all treatment groups at a low incidence (about 5% of live fetuses) and in no case was the total incidence of malformations greater than 10%. There was little correlation between indications of maternal toxicity and the adverse outcomes of pregnancy, suggesting that TPA has direct embryotoxic effects. The relatively low incidence of anomalies is considered a paradox in light of the potent effects of TPA on cellular processes critical to embryogenesis.
D000014:Abnormalities, Drug-Induced; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D007668:Kidney / Q000002:abnormalities*; D051379:Mice; D008815:Mice, Inbred Strains; D010704:Phorbols / Q000633:toxicity*; D011247:Pregnancy; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D010704:Phorbols; D013755:Tetradecanoylphorbol Acetate