Hemeoxygenase expression in human placenta and placental bed implies a role in regulation of trophoblast invasion and placental function

The purpose of this study was to examine the expression of hemeoxygenases H O-1 and HO-2, which are responsible for the production of carbon monoxide ( CO), in the human placenta and placental bed and to determine the role of i nhibitors of HO on placental perfusion pressure. We hypothesized that HO is expressed within the placenta and that invading cytotrophoblast cells (CTB ) express HO isoforms. The expression of HO-1 and HO-2 was studied on place nta and placental bed biopsies, obtained using a transcervical sampling tec hnique, from normal human pregnancies between 8 and 19 wk gestation and at term. in the placenta, HO-2 immunostaining was prominent in syncytiotrophob last in the first trimester and reduced toward term (P<0.0005). HO-2 endoth elial immunostaining was weak in the first trimester, but increased by term (P<0.0005). Within the placental bed, HO-2 was expressed by CTB in cell co lumns, the cytotrophoblast shell, and cell islands. Both intravascular CTB and interstitial CTB expressed HO-2. HO-1 immunostaining was low in the pla centa but intense on the CTB within the placental bed. A striking feature w as the absence of HO-1 from the proximal layers of cell columns, with stron g expression on the more distal CTB layers of the cell columns. in placenta l perfusion studies, a significant dose-dependent increase in perfusion pre ssure was observed in the presence of zinc protoporphyrin, an inhibitor of HO. These results suggest a role for CO in placental function, trophoblast invasion, and spiral artery transformation. Hemeoxygenase expression in hum an placenta and placental bed implies a role in regulation of trophoblast i nvasion and placental function.