The mechanisms of deficient placentation in the first trimester remain poorly understood, although apoptosis,
hypoxia, and oxidative stress have been implicated. High uterine artery Doppler resistance indexes (RIs) are predictive of placental complications of pregnancy, such as
preeclampsia,
fetal growth restriction, and
stillbirth. We provide evidence that even in the first trimester, pregnancies with high uterine artery Doppler RI demonstrate alterations in placental gene and
protein expression. Apoptosis was significantly higher in high RI placental tissue, as determined by Western blot analysis of cleaved
poly (ADP-ribose) polymerase and
caspase 3.
Protein expression of the trophoblast survival
factor insulin-like growth factor-2 was significantly lower. Both high and normal RI placentas showed evidence of
hypoxia and oxidative stress with expression of
hypoxia-inducible factors 1α and 2α,
heat shock protein 70, presence of
nitrotyrosine residues, and lipid peroxidation. We observed no exaggerated placental
hypoxia or oxidative stress associated with high RI pregnancies. High RI placental tissue demonstrated an altered balance of
antioxidant enzyme activity.
Hypoxia and oxidative stress appear to be a physiological state in early pregnancy; our data did not support the hypothesis that they are associated with deficient placentation in the first trimester. Higher levels of apoptosis, reduced
insulin-like growth factor-2 expression, and altered
antioxidant defenses may contribute to abnormal placentation and the later development of
pregnancy complications, such as
preeclampsia,
fetal growth restriction, and
stillbirth.