Effects of methamphetamine on rat embryos cultured in vitro.

Wistar rat embryos were explanted on day 10.5 of gestation and exposed in vitro to methamphetamine (MAMP) at a concentration of 0.1, 0.2, 0.4, 0.6, or 0.8 mM for 24 h, and the direct teratogenic effects of the drug on rat embryos were examined. The viability of cultured embryos was not affected by the MAMP treatment. The yolk sac diameter was reduced at MAMP concentrations of 0.6 and 0.8 mM. The crown-rump length and the somite number of the embryos decreased significantly and dependently on the MAMP concentrations at 0.4-0.8 mM. The protein content was also significantly reduced at 0.4-0.8 mM. The developmental score was decreased in a concentration-dependent manner. The frequency of malformed embryos significantly increased at 0.6 and 0.8 mM. The malformations induced in treated embryos included microcephaly, neural tube defects, incomplete rotation of the body axis, and tortuous spinal cord. Abnormal histological changes such as derangement and necrosis in the neuroepithelial tissue were observed in embryos exposed to high concentration of the drug. Our results revealed the direct embryotoxic and teratogenic effects of MAMP in the rat.