Diabetes in pregnancy: influence of genetic background and maternal diabetic state on the incidence of skeletal malformations in the fetal rat.
Female Sprague-Dawley rats from two different substrains (denoted U and H rats) were made manifest diabetic (MD) with a single iv injection of streptozotocin 2-4 weeks before mating. In some MD animals insulin treatment was started 1-3 weeks before mating (denoted MDI rats) and in a majority of these animals the treatment was interrupted during two days of pregnancy, i.e. gestational days 2 + 3, 4 + 5, 6 + 7, 8 + 9 or 10 + 11. The pregnant rats were killed on gestational day 20. The offspring of MD and MDI rats of the U substrain showed skeletal malformations (micrognathia and sacral dysgenesis) at a rate up to 19%, whereas the MD and MDI fetuses of the H strain did not display any skeletal malformations. Offspring of the U strain with sacral dysgenesis exhibited lack of a tail and no staining of osseous and cartilagenous tissue in the sacral-caudal region, suggesting total absence of vertebrae. The offspring of the diabetic U rats tended to be more readily resorbed, were smaller and tended to have slightly larger placentae than those of the diabetic H rats. The severity of the diabetic state in pregnant and nonpregnant female rats--as reflected by body and kidney weights, blood levels of HbA1c, carbohydrate and lipid metabolites--did not differ significantly between the U and H rats. These results are in concert with the notion that congenital malformations result from a teratogenic insult in a genetically predisposed organism. The described malformation-prone rat strain (U) may be a suitable model for the future elucidation of teratological mechanisms in diabetic pregnancy.
Eriksson
U J
UJ
Dahlström
V E
VE
Lithell
H O
HO
D000818:Animals; D001835:Body Weight; D001842:Bone and Bones / Q000002:abnormalities* / Q000196:embryology; D000013:Congenital Abnormalities / Q000209:etiology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000235:genetics*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D008431:Maternal-Fetal Exchange; D009929:Organ Size; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000150:complications / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains
D006442:Glycated Hemoglobin