The effects of ochratoxin A on postimplantation rat embryos in culture.

The mycotoxin, ochratoxin A (OA), is a potent in vivo teratogen. Studies were performed to determine the in vitro effects of OA on postimplantation rat embryos. Embryos were explanted from pregnant Sprague-Dawley rats on day 10 of gestation and were cultured (within the yolk sac) for 45 hr in gassed rat serum containing OA at concentrations between 0 and 300 micrograms/mL. Gross morphology, histopathology and protein and DNA content of embryos were evaluated. An OA concentration-dependent reduction in yolk sac diameter, crown-rump length, somite number count, and protein and DNA content was observed. Ochratoxin A treatment also resulted in an increase in the incidence of defective embryos. Malformations included: growth retardation, hypoplasia of the telencephalon, poor flexion, stunted limb bud development, underdeveloped sensory primordia and decreased mandibular and maxillary size. Histological examination demonstrated extensive OA-induced necrosis of embryonal mesodermal structures and neuroectoderm. Thus, the rat embryo in culture is a sensitive indicator of OA toxicity and may be useful for predicting developmental hazards associated with this mycotoxin.