Trophoblastic Oxidative Stress in Relation to Temporal and Regional Differences in Maternal Placental Blood Flow in Normal and Abnormal Early Pregnancies

Abstract

Onset of the maternal-placental circulation was studied by Doppler ultrasonography in 65 pairs of agematched normal and abnormal pregnancies. In normal pregnancies intervillous blood flow increased with gestational age, being detected in 9 of 25 cases at 8 to 9 weeks but in 18 of 20 at 12 to 13 weeks (P ‫؍‬ 0.001). By contrast, in abnormal pregnancies flow was detected in nearly all cases (22 of 25) at 8 to 9 weeks (P < 0.001). In addition, regional differences were observed between the groups. Early flow was restricted to the peripheral regions of most normal placentas (P < 0.001), whereas in missed miscarriages it was most common in central regions or throughout the placenta (P < 0.05 and P < 0.001, respectively). Immunoreactivity for heat shock protein 70 and nitrotyrosine residues was greater in samples from peripheral than from central regions of normal placentas (P ‫؍‬ 0.028 and P ‫؍‬ 0.019, respectively), and from missed miscarriages compared to controls (P ‫؍‬ 0.005 and P ‫؍‬ 0.001, respectively). Our results indicate that oxidative damage to the trophoblast, induced by premature and widespread onset of the maternal placental circulation secondary to shallow trophoblast invasion, is a key factor in early pregnancy loss. High oxygen concentrations in the periphery of normal early placentas may similarly induce local regression of the villi, leading to formation of the chorion laeve. Placentation in the human is characterized by diffuse infiltration of the endometrium and the inner third of the myometrium by extravillous trophoblast cells.

Pro- and antiinflammatory cytokines in threatened miscarriages

“…As the gestational sac grows during fetal life, the villi that are associated with the decidua capsularis surrounding the amniotic sac degenerate and form the chorion leave, whereas villi that are associated with the decidua basalis proliferate and form the definitive placenta. 7 We previously have shown that the underlying uteroplacental circulation in the center of the primitive placenta is plugged, whereas in periphery the mouth of the spiral arteries are never plugged by the trophoblastic shell, which allows limited maternal blood flow to enter the marginal zone of placenta from 8-9 weeks of gestation. 8 This leads to higher local O 2 concentration at a stage of pregnancy when the trophoblast possesses low concentrations of the main antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase.…”

“…8 This leads to higher local O 2 concentration at a stage of pregnancy when the trophoblast possesses low concentrations of the main antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase. 7 Focal trophoblastic oxidative damage and progressive villous degeneration trigger the formation of fetal membranes, which remodels the uteroplacental interface. First-trimester vaginal bleeding has been associated with increased maternal levels of free serum ␤-hCG, 41 possibly because of a rise in hCG transfer into the maternal circulation because of the disruption of the maternofetal interface.…”

“…6 The pathophysiology of TM is linked to bleeding from uteroplacental vessels at the margin of the placenta with blood accumulating between the chorionic membrane and uterine wall. 7 The formation of a subchorionic hematoma may disrupt the placental bed. If the hematoma expands to the rest of the placental mass, it will induce complete miscarriage within a week of the first symptoms.…”

“…8 If bleeding is limited or happens close to the internal cervical os and is evacuated, the pregnancy may continue; however, this can lead to a chronic inflammatory reaction within the decidua and membranes. 7,8 Within this context, TM is associated with a higher incidence of preterm labor, prelabor rupture of membranes, placental abruption, fetal growth restriction, and low birthweight. 2,[9][10][11][12][13][14][15][16][17][18] A strong association exists between maternal T helper-1 (Th1)-type immunity and pregnancy loss, whereas a shift towards Th2-type cytokine response has been observed in successful pregnancy.…”

Gestation linked radical oxygen species fluxes and vitamins and trace mineral deficiencies in the ruminant

“…Inefficient invasion of the spiral arteries can induce an unresolved placental oxidative stress and lead to pre-eclampsia [5,8,22]. Due to the occlusion of the maternal vessels by trophoblasts, the initial gradient of oxygen partial pressure between the mother (where it amounts to around 50-100 mm Hg) and the embryo (where it amounts to around 14 mm Hg) is maintained after the 8th week of gestation and evolves slowly to 39.6 mm Hg at a gestational age of 10 weeks [38,52,54], the complete transformation of the spiral arteries being achieved only between weeks 18 and 20 of gestation [55]. In the conceptus, the low initial oxygen partial pressure evolves only slowly between the 10th and 16th week of pregnancy from 64.3 to 73.2 mm Hg at the level of decidua, from 25.6 to 56.2 mm Hg at the level of the placenta, and, remains unchanged during this interval at the level of the coelomic fluid, i.e.…”