Folic acid supplementation affects ROS scavenging enzymes, enhances Vegf-A, and diminishes apoptotic state in yolk sacs of embryos of diabetic rats.
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.
Zabihi
Sheller
S
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. sheller.zabihi@mcb.uu.se
Eriksson
Ulf J
UJ
Wentzel
Parri
P
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
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