title: Folic acid supplementation affects ROS scavenging enzymes, enhances Vegf-A, and diminishes apoptotic state in yolk sacs of embryos of diabetic rats.
abstract: We aimed to investigate the extent to which maternal diabetes with or without folic acid (FA) supplementation affects mRNA levels and protein distribution of ROS scavenging enzymes, vascular endothelial growth factor-A (Vegf-A), folate binding protein-1 (Folbp-1), and apoptosis-associated proteins in the yolk sacs of rat embryos on gestational days 10 and 11. Commencing at conception and throughout pregnancy, half of the streptozotocin-diabetic and half of the control rats received daily FA injections. Maternal diabetes impaired vascular morphology and decreased CuZnSOD and GPX-1 gene expression in yolk sacs. Maternal diabetes also increased the levels of CuZnSOD protein, increased the Bax/Bcl-2 protein ratio and decreased Vegf-A protein distribution. FA treatment normalized vascular morphology, decreased mRNA levels of all three SOD isoforms and increased Vegf-A mRNA levels, rectified CuZnSOD protein distribution and Bax/Bcl-2 ratio. A teratogenic diabetic environment produces a state of vasculopathy, oxidative stress, and mild apoptosis in the yolk sac. FA administration normalizes vascular morphology, diminishes apoptotic rate, and increases Vegf-A gene expression and protein distribution in the yolk sac of diabetic rats.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. sheller.zabihi@mcb.uu.se
authors.forename: Sheller
authors.initials: S
authors.lastname: Zabihi
authors.forename: Ulf J
authors.initials: UJ
authors.lastname: Eriksson
authors.forename: Parri
authors.initials: P
authors.lastname: Wentzel
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000196:embryology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005492:Folic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005865:Gestational Age; D005979:Glutathione Peroxidase / Q000378:metabolism; D050938:Glycine N-Methyltransferase / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D015017:Yolk Sac / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; C467498:vascular endothelial growth factor A, rat; D005492:Folic Acid; D010088:Oxidoreductases; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D050938:Glycine N-Methyltransferase; C494512:Gnmt protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3