Heme oxygenases in pregnancy II: HO-2 is downregulated in human pathologic pregnancies.
OBJECTIVE
We previously reported a diminished expression of the heme-degrading enzymes heme oxygenases (HO)-1 and HO-2 in decidua and placenta from mice undergoing Th1-mediated abortion, strongly indicating the protective effect of HO in murine pregnancy maintenance. Here we investigated whether the expression of HO-1 and HO-2 is also reduced at the feto-maternal interface of pathologic human pregnancies.


METHODS
Immunohistochemistry was used to detect HOs expression in placental and decidual first-trimester tissue from patients with: spontaneous abortion (n = 14), choriocarcinoma (n = 14), hydatidiform mole (H-mole) (n = 12), compared with normally progressing pregnancies (n = 15). Further, we investigated early third-trimester decidual and placental tissue from patients with pre-eclampsia (n = 13) compared with fetal growth retardation (n = 14) as age-matched controls.


RESULTS
In first trimester tissue, we observed a significant reduction of HO-2 expression in invasive trophoblast cells, endothelial cells, and syncytiotrophoblasts in samples from patients with spontaneous abortion compared with normal pregnancy. H-mole samples showed a diminished expression of HO-2 in invasive trophoblast cells and endothelial cells in comparison with NP, whereas choriocarcinoma samples showed no significant differences compared with the control. In third trimester tissue, HO-2 was also reduced in syncytiotrophoblasts and invasive trophoblast cells from pre-eclampsia compared with samples from fetal growth retardation. HO-1 expression was diminished in all pathologies investigated; however, the differences did not reach levels of significance.


CONCLUSIONS
Our data indicate that HOs play a crucial role in pregnancy and low expression of HO-2, as observed in pathologic pregnancies, may lead to enhanced levels of free heme at the feto-maternal interface, with subsequent upregulation of adhesion molecules, allowing enhanced inflammatory cells migration to the feto-maternal interface.
D000022:Abortion, Spontaneous / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D000328:Adult; D002822:Choriocarcinoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D003656:Decidua / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D015536:Down-Regulation; D042783:Endothelial Cells / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D005260:Female; D005317:Fetal Growth Retardation / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D006828:Hydatidiform Mole / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D007633:Keratins / Q000032:analysis; D008565:Membrane Proteins; D010920:Placenta / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D011225:Pre-Eclampsia / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000201:enzymology* / Q000378:metabolism; D014327:Trophoblasts / Q000737:chemistry / Q000201:enzymology / Q000473:pathology
D008565:Membrane Proteins; D007633:Keratins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2