Comparative embryotoxicity of selenite and selenate: uptake in murine embryonal and fetal tissues and effects on blastocysts and embryonic cells in vitro.
The placental transfer and distribution pattern of selenium (Se) in embryonic and fetal tissues after intravenous injection of Na2(75)SeO3 (Se4+) or Na2(75)SeO4 (Se6+) has been investigated in mice in early, mid, and late pregnancy by use of whole-body autoradiography combined with gamma-counting. The given doses correspond to 45 micrograms Se/kg. In order to compare the direct toxicity in early embryonic stages, the two valence forms were studied by using in vitro systems with (1) mouse blastocysts and (2) chick embryo fibroblasts, differentiating into chondrocytes. The embryonic and fetal uptake after administration of Se4+ and Se6+ was almost identical. The placental transfer of Se was restricted but, nevertheless, increased with time after dosing and with progression from embryonic through fetal stages thereby suggesting active placental transfer. The highest uptake in the embryo was observed in the neuro-epithelium while the eye, liver and skeleton dominated the distribution pattern in the fetal period. Selenite (Se4+) was more toxic than selenate (Se6+) in the in vitro system, in which embryonic mesenchymal limb bud cells differentiated into chondrocytes, as well as in the blastocyst culture system. The results may suggest a direct effect of Se in the embryo as explanation to reported malformations in experimental studies.
Danielsson
B R
BR
Department of Toxicology, Uppsala University, Sweden.
Danielson
M
M
Khayat
A
A
Wide
M
M
D000818:Animals; D001755:Blastocyst / Q000187:drug effects* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D002642:Chick Embryo; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000473:pathology; D005314:Embryonic and Fetal Development; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D008431:Maternal-Fetal Exchange / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D064586:Selenic Acid; D012643:Selenium / Q000493:pharmacokinetics / Q000633:toxicity*; D018036:Selenium Compounds; D018038:Sodium Selenite; D014018:Tissue Distribution
D018036:Selenium Compounds; D012643:Selenium; D018038:Sodium Selenite; D064586:Selenic Acid