Background: PE affects ~2% of pregnancies and is associated with generalised endothelial cell dysfunction. Antioxidant selenoproteins may limit such effects. Serum selenium is lower in mothers and babies affected by PE and associated with lower activity of the selenoprotein glutathione peroxidases. Other selenoproteins, the iodothyronine deiodinases (IDs; D2 and D3) regulate fetal thyroid hormone synthesis. The IDs utilise selenium preferentially; we have reported similar triiodothyronine (T3) and thyroxine (T4) in both maternal and umbilical serum from NT and PE pregnancies. We hypothesised that ID enzyme activities would be conserved in PE placentae.
Design: Hospital based cross-sectional study with full ethics approval. Placental biopsies were obtained at delivery from 3 sites; 1 cm from cord insertion (near), midway between insertion and edge (middle) and 1 cm from the edge (outer) from 27 NT and 21 PE European women. Homogenate D2 and D3 activities were determined by HPLC analysis following formation of the radioactive T4 and T3 respectively. Protein localisation was confirmed by immunohistochemistry.
Results: D3 enzyme activity was identified in all placentae; immunoreactivity was confirmed in the syncytiotrophoblasts. Friedman Repeated Measures demonstrated a significant (P=0.034) gradient in placental D3 activity (Table 1) in NT but not PE; activity in individual sampling sites did not differ between NT and PE. Neither D2 protein expression nor activity were detected.
|D3 activity (fmol/min per mg protein) median (interquartiles)|
|Near||7.6 (4.3, 12.5)||5.2 (3.0, 11.8)|
|Middle||4.9 (3.3, 8.3)||4.3 (3.1, 8.8)|
|Outer||4.8 (3.2, 7.5)||5.3 (2.9, 10.3)|
Conclusions: These data show no effect of PE at delivery on placental D3 activity which corroborates our earlier data showing comparable mRNA expression and similar (T3) and (T4) in NT and PE samples. The difference in activity across the placental bed only in NT pregnancy suggests a possible blunting in enzyme regulation in PE which may relate to the lower tissue oxygenation at the periphery of the placenta.
Acknowledgment: LOK was generously funded by an Early Career Grant and HDM by a Lab Visit Grant from the Society for Endocrinology.