Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure.
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.
Jauniaux
E
E
Academic Department of Obstetrics and Gynaecology, University College London, London, United Kingdom.
Watson
A L
AL
Hempstock
J
J
Bao
Y P
YP
Skepper
J N
JN
Burton
G J
GJ
D000022:Abortion, Spontaneous / Q000209:etiology; D001158:Arteries / Q000502:physiology; D004350:Drug Residues / Q000378:metabolism; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000648:ultrastructure; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000235:genetics; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D010920:Placenta / Q000098:blood supply* / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy / Q000502:physiology*; D011261:Pregnancy Trimester, First; D012333:RNA, Messenger / Q000378:metabolism; D012039:Regional Blood Flow; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; C002744:3-nitrotyrosine; D014443:Tyrosine; D010088:Oxidoreductases; D010100:Oxygen