Effect of lithium on rat embryos in culture: Growth, development, compartmental distribution and lack of a protective effect of inositol

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Abstract
Lithium chloride (LiCl) was tested at various concentrations (50, 100, 150 and 200 μg/ml) using a rat whole-embryo culture system beginning on gestation day 9.5 (headfold stage) in order to establish a concentration-response relationship. Open neural tubes — as described in former publications (Tesh 1988) — were not induced by lithium. A significant reduction of embryonic growth and development occurred at the lowest concentration tested (50 μg/ml). Clear-cut dysmorphogenetic effects (absence of the eye cup, kink in the spinal anläge, “blebs” at the rostral head region) occurred at a concentration of 150 μg/ml LiCl. LiCl concentrations in the embryo, visceral yolk sac, exocoelomic fluid and medium were determined after the embryos had been cultured for 48 h in the presence of a moderately embryotoxic dose of LiCl (3.5 mEq/l or 150 μg/ml). Medium supplementation withmyo-inositol in different concentrations was ineffective in antagonizing the embryotoxicity induced by LiCl.