3-nitrotyrosine and Abortion--Spontaneous

To investigate the role played by platelet nitric oxide (NO) metabolism in patients with spontaneous miscarriage (SM) and recurrent spontaneous miscarriage (RSM) compared with healthy pregnant women.. Retrospective case-control study.. Patients and controls in an academic research environment.. None.. Thirty singleton pregnant women who experienced SM, nine singleton pregnant women who presented with RSM, and 30 singleton healthy pregnant women matched for age, parity, and gestational age were enrolled.. NO levels and peroxynitrite (ONOO(-)) production; moreover, inducible NO synthase (iNOS), endothelial NO synthase (eNOS), and nitrotyrosine expression (N-Tyr) were observed in the same samples.. A significant increase was shown in platelet NO and ONOO(-) levels and in iNOS and N-Tyr both in SM and in RSM pregnant women compared with controls.. The data herein reported imply that a modified NO pathway might play a key role in the physiological changes of advancing gestation but may also contribute to the pathophysiology of spontaneous miscarriage. Thus, any factors balancing NO metabolism might be useful in the treatment of miscarriage, thus reducing the substantial morbidity and associated mortality.

Topics: Abortion, Spontaneous; Adult; Blood Platelets; Case-Control Studies; Female; Humans; Nitric Oxide; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Peroxynitrous Acid; Pregnancy; Pregnancy Trimester, First; Retrospective Studies; Tyrosine

The aim was to measure changes in the oxygen tension within the human placenta associated with onset of the maternal arterial circulation at the end of the first trimester of pregnancy, and the impact on placental tissues. Using a multiparameter probe we established that the oxygen tension rises steeply from <20 mmHg at 8 weeks of gestation to >50 mmHg at 12 weeks. This rise coincides with morphological changes in the uterine arteries that allow free flow of maternal blood into the placenta, and is associated with increases in the mRNA concentrations and activities of the antioxidant enzymes catalase, glutathione peroxidase, and manganese and copper/zinc superoxide dismutase within placental tissues. Between 8 to 9 weeks there is a sharp peak of expression of the inducible form of heat shock protein 70, formation of nitrotyrosine residues, and derangement of the mitochondrial cristae within the syncytiotrophoblast. We conclude that a burst of oxidative stress occurs in the normal placenta as the maternal circulation is established. We speculate that this may serve a physiological role in stimulating normal placental differentiation, but may also be a factor in the pathogenesis of pre-eclampsia and early pregnancy failure if antioxidant defenses are depleted.

Topics: Abortion, Spontaneous; Arteries; Drug Residues; Female; HSP70 Heat-Shock Proteins; Humans; Mitochondria; Oxidative Stress; Oxidoreductases; Oxygen; Partial Pressure; Placenta; Pregnancy; Pregnancy Trimester, First; Regional Blood Flow; RNA, Messenger; Tyrosine