MECHANISM OF TRIMETHYLAMINE-INDUCED INHIBITION OF MACROMOLECULAR-SYNTHESIS BY MOUSE EMBRYOS IN CULTURE

The effects of trimethylamine (TMA) on uptake mechanisms and lysosomal function were studied in mouse embryos, isolated yolk sacs and limb b uds. TMA at 0.75 mM did not inhibit uptake of [C-14]sucrose by yolk sa cs of day 9 embryos or by day 15 isolated yolk sacs but did inhibit up take of I-125-labelled bovine serum albumin ([I-125]BSA) by day 15 iso lated yolk sacs. Concentrations of TMA up to 2.5 mM did not inhibit ly sosomal degradation of [I-125]BSA by isolated yolk sacs, as judged by the release of trichloroacetic acid (TCA)-soluble radioactivity into t he culture media. The inhibition of [I-125]BSA uptake induced by TMA w as reversible on removal of TMA. When day 8 embryos were cultured in s erum containing [H-3]leucine-labelled proteins, uptake and incorporati on of radioactivity in 0.75 mM TMA-treated embryos was 47 and 44%, res pectively, of that in untreated controls. TMA at 0.75 mM did not inhib it the uptake and incorporation of free [H-3]leucine into embryonic pr otein nor the amount of free [H-3]leucine taken up or incorporated int o protein by day 12 isolated limb buds. It is concluded that the reduc ed macromolecular synthesis in embryos exposed to TMA is due to an inh ibition of receptor-mediated uptake of nutrients by the yolk sac.