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Expression of hypoxia-related transcripts defines histological changes in the term human placenta

      Objective

      Human villous trophoblast determines transport of oxygen, nutrients, and waste products between fetal and maternal blood. Using oligonucleotide microarray, we have previously identified a set of gene products that exhibit enhanced expression in hypoxic human trophoblasts. We hypothesized that expression of this transcript set correlates with histological changes observed in the term placenta.

      Study design

      We biopsied nine different sites from term human placentas (n = 6), obtained after normal delivery. These sites spanned regions from the placental disk center to the lateral border, and from the basal to the chorionic plate. A pathologist blinded to biopsy site evaluated the histology at each site and graded the level of villous maturation, syncytial knot formation, and fibrin deposition. Quantitative PCR was used for determination of gene expression for each site and for correlation with histological grade.

      Results

      Histological changes characteristic of hypoperfused villi were abundant near the chorionic plate, particularly at the placental lateral edge. The expression (mean±SE) of the growth factors VEGF (1.6±0.6) and CTGF (2.3±0.8), and the cytoskeleton proteins lamininA3 (1.9±1) and alpha-tubulin (2.9±0.9), as well as the stress response/oncogene RTP (1.4±0.3) and RAD (1.9±0.7), was enhanced in the subchorionic lateral edge, compared to the central basal site. Using Spearman rank test, we found a significant correlation between histological grade and gene expression for VEGF (P = 0.03), lamininA3 (P = 0.02), alpha-tubulin (P = 0.03), RTP (P = 0.03), and RAD (P = 0.002).

      Conclusion

      Hypoxia-related transcript expression defines histological changes characteristic of hypoxic villi. Assessing this transcript set in villi may shed light on villous response to hypoxia and potentially become a novel tool to characterize placental injury in pregnancies complicated by placental hypoperfusion and IUGR.
      (Supported by NIH ES-11597 and HD-29190.)