Effects of methyl mercury on murine fetal amino acid uptake, protein synthesis and palate closure.
Methylmercury (MeHg: 5 mg Hg/kg maternal body weight) in 0.13 M NaCl, 0.01 M NaH2PO4-Na2HPO4, pH 7.4 (PBS) administered to gravid CFW mice on day 12, hour 6 (12(6)) of gestation induced a high incidence of cleft palate in fetuses examined on days 15(6) (72%), 16(6) (62%) and 17(6) (40%). Palate closure (100%) in PBS control animals occurred by 14(10). One day post MeHg administration, total fetal protein was decreased 22% while DNA content was unaltered. Protein was maximally decreased (28%) on 14(6) and, thereafter, returned toward control levels. Alterations in DNA content followed a similar pattern; but the maximal decrease (32%) occurred on 15(6). The rate of fetal protein synthesis was depressed 5% at 12(9) and between 20% to 26% from this time to 13(6) (end of observation). The agreement between the calculated decrease in protein synthesis (19%) and the measured decrease in protein content (22%) suggests that a reduction in protein synthesis is responsible for the decreased fetal protein content. Placental blood flow and fetal water space, measured with 3H--H2O at 12(18), were not affected by MeHg treatment. However, fetal free amino acid concentrations at 12(18) were generally decreased (alanine, 23.0%; valine, 9.7%; methionine, 22.6%; isoleucine, 12.0%; leucine, 18.2%) while uptake of the non-metabolizable amino acid, 14C-cycloleucine, was decreased 23%. From this, it is concluded that the growth inhibitory effects of MeHg are related, at least in part, to impaired placental/fetal transfer of amino acids.
D000014:Abnormalities, Drug-Induced; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002972:Cleft Palate / Q000139:chemically induced*; D004247:DNA / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism*; D008431:Maternal-Fetal Exchange; D008767:Methylmercury Compounds / Q000009:adverse effects*; D051379:Mice; D010159:Palate / Q000196:embryology; D010920:Placenta / Q000378:metabolism; D010922:Placenta Diseases / Q000139:chemically induced; D011247:Pregnancy; D014176:Protein Biosynthesis
D000596:Amino Acids; D008767:Methylmercury Compounds; D004247:DNA