title: Gamma-linoleic acid and ascorbate improves skeletal ossification in offspring of diabetic rats.
abstract: Maternal diabetes causes a range of complications in offspring, including reduced skeletal ossification. This study examined whether feeding gamma-linoleic acid (GLA) and ascorbate, alone or in combination, to diabetic pregnant rats improves skeletal development in their offspring. In addition, Ca(2+) concentration was monitored in maternal plasma and fetal tissue, as well as placental mRNA expression of calbindin-D(9k). Female rats rendered diabetic with streptozotocin were fed GLA (500 mg/kg/d), ascorbate (290 mg/kg/d), ascorbyl-GLA (790 mg/kg/d), or GLA and ascorbate (500 and 290 mg/kg/d, respectively) throughout pregnancy. Fetal skeletons were studied after alizarin red staining. Fewer ossification centers were observed in offspring of diabetic rats compared with offspring of control rats (68 +/- 4% of control, p = 0.01). An almost complete restoration of ossification occurred with all the treatments (92-95 +/- 3% of control). The effects of treatment on fetal ossification could not be explained by altered maternal plasma Ca(2+) concentrations or by mRNA expression of the placental Ca(2+)-transporting protein calbindin-D(9K). We conclude that GLA and/or ascorbate treatment was effective against diabetes-induced fetal ossification defects by a mechanism not related to placental Ca(2+) supply.
authors.affiliation: School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
authors.forename: Rattana
authors.initials: R
authors.lastname: Braddock
authors.forename: C Martin
authors.initials: CM
authors.lastname: Simán
authors.forename: Katherine
authors.initials: K
authors.lastname: Hamilton
authors.forename: Hugh O
authors.initials: HO
authors.lastname: Garland
authors.forename: Colin P
authors.initials: CP
authors.lastname: Sibley
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use*; D001842:Bone and Bones / Q000737:chemistry / Q000187:drug effects / Q000196:embryology; D002118:Calcium / Q000032:analysis / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D005314:Embryonic and Fetal Development / Q000187:drug effects; D044943:Fatty Acid Desaturases / Q000172:deficiency; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D005951:Glucose Tolerance Test; D007328:Insulin / Q000032:analysis; D050602:Linoleoyl-CoA Desaturase; D008274:Magnesium / Q000032:analysis / Q000378:metabolism; D008297:Male; D008431:Maternal-Fetal Exchange; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D010012:Osteogenesis / Q000187:drug effects*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000097:blood; D051381:Rats; D017382:Reactive Oxygen Species; D013311:Streptozocin
chemical_list: D007328:Insulin; D017382:Reactive Oxygen Species; D013311:Streptozocin; D044943:Fatty Acid Desaturases; D050602:Linoleoyl-CoA Desaturase; D008274:Magnesium; D001205:Ascorbic Acid; D002118:Calcium