Increased nitrotyrosine in the diabetic placenta: evidence for oxidative stress.
OBJECTIVE
To evaluate the presence of nitrotyrosine (NT) residues in placental villous tissue of diabetic pregnancies as an index of vascular damage linked to oxidative stress.


METHODS
Villous tissue was collected and flash frozen after delivery from 10 class C and D IDDM patients (37.9+/-3.2 weeks) and 10 normotensive pregnant individuals (37.5+/-3.8 weeks). Serial sections of tissue were immunostained with specific antibodies to NT, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and manganese superoxide dismutase (MnSOD). Sections were scored for intensity of immunostaining (0-3) by three observers blinded to the identity of tissue.


RESULTS
All tissues demonstrated immunostaining for eNOS in both syncytiotrophoblast and stem villous vascular endothelium with no apparent differences between groups. Immunostaining for iNOS was seen in the villous stroma, but again was not different between the two groups. Significantly more intense NT staining was apparent in vascular endothelium and villous stroma (both P < 0.02) of diabetic placentas. The endothelium of large villous vessels of diabetic tissues also showed more intense immunostaining for MnSOD (P < 0.01).


CONCLUSIONS
In these diabetic pregnancies, we were unable to show increased eNOS, unlike previous findings in preeclamptic pregnancies. The presence of NT may indicate vascular damage in the diabetic placenta due to peroxynitrite action formed from increased synthesis/interaction of nitric oxide and superoxide. The apparently paradoxical increase in MnSOD expression may be an adaptive response to increased superoxide generation.
Maternal and Fetal Medicine Section, Institute of Medical Genetics, University of Glasgow, Yorkhill, Scotland, UK.
F
F
Lyall
J L
JL
Gibson
I A
IA
Greer
D E
DE
Brockman
A L
AL
Eis
L
L
Myatt
D015415:Biomarkers; D002824:Chorionic Villi / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress; D010920:Placenta / Q000166:cytology / Q000201:enzymology / Q000473:pathology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011254:Pregnancy in Diabetics / Q000378:metabolism* / Q000473:pathology; D012016:Reference Values; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
D015415:Biomarkers; D006442:Glycated Hemoglobin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D014443:Tyrosine; C002744:3-nitrotyrosine; C496319:NOS2 protein, human; C496314:NOS3 protein, human