Low molecular weight dermatan sulphate (Desmin 370) does not cross the ovine placenta.
Transplacental passage of the low molecular weight dermatan sulphate Desmin 370 was investigated in pregnant sheep, using 125I-labelled Desmin 370 to optimize the sensitivity of the study. Chronically catheterized cross-bred pregnant ewes at approximately 120 d gestation received 3700 kBq 125I-labelled Desmin 370 with 1 mg/kg carrier unlabelled Desmin 370 intravenously. Early clearance from the maternal circulation was biexponential, and the volume of distribution corresponded closely with the theoretical value for distribution in total body water. Soon after injection low levels of radioactivity were detected in the fetal circulation and accumulated over the next 2 h, so that as the concentration of 125I-Desmin 370 in the maternal circulation declined with time the fetal level of radiolabel rose to represent a significant concentration in relation to that in the mother. Radioactivity was also excreted into the fetal urine. However, while 50% of the radiolabelled material present in maternal plasma 150 min post-injection was intact Desmin 370 and the remaining 50% represented degradation products, fetal urine contained only these fragments. By contrast, intact Desmin 370 was readily excreted into fetal urine after direct introduction to the fetal circulation. Thus molecules of intact Desmin 370 with anticoagulant activity cannot cross the ovine placenta, and low molecular weight dermatan sulphates may be valuable for prophylaxis and treatment of thrombotic disease during pregnancy.
Dawes
J
J
Heart Research Institute, Camperdown, NSW, Australia.
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D000818:Animals; D003871:Dermatan Sulfate / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D008970:Molecular Weight; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D012756:Sheep
D003871:Dermatan Sulfate