Caffeine exposure in utero in rats is known to result in intrauterine
growth retardation and lowered birth weight as well as changes to beha
viour and brain biochemistry. We have investigated whether caffeine's
embryotoxicity is a result of the events associated with increased hsp
synthesis, i.e., disruption to normal protein synthesis. Caffeine (30
mg/kg) was administered orally to pregnant rats as single or repeated
doses. Embryos were removed 3 h after dosing on gestation day (GD) 9,
10, 11 and 12 and total embryonic protein and RNA analysed. There was
no change in the mRNA or protein levels of hsp 88, 71/73, and 25 afte
r acute or chronic treatment. To separate the direct effect of caffein
e from those mediated through the mother, whole rat embryo culture was
used. Caffeine (50 mug/ml) for 90 min did not increase hsp 88, 73 or
25 mRNA levels in 9.5,10.5 and 11.5 GD cultured embryos. We conclude t
hat in vivo or in vitro treatment of 9-12 GD mt embryos with moderate
to high doses of caffeine does not increase the synthesis of the major
mammalian hsps. Hence, hsp induction is unlikely to play a role in th
e embryotoxic actions of caffeine.