Erythropoietin and erythropoietin receptor expression in normal and disturbed pregnancy

Erythropoietin (Epo) is known to regulate the number of circulating erythrocytes. Epo receptor (Epo-R) expression is limited to few organs including the uterus. We investigated differences in Epo and Epo-R expression in normal and disturbed first trimester human pregnancy.

Placental tissue was obtained from normal human pregnancy, abortion and hydatidiform mole during the first trimester of pregnancy. Epo and Epo-R expression was investigated by Immunohistochemistry and real time PCR (TaqMan). The intensity and distribution patterns of Epo and Epo-R expression were evaluated by using a semi-quantitative method (immunoreactive score) as previously described.

Epo-R expression was upregulated in the villous trophoblast (VT) of abortive tissue (p=0.002) as compared to normal pregnancy. This was further confirmed on mRNA level. With regard to mole pregnancy, Epo-R expression was also significantly increased in the VT (p<0.001). In extravillous trophoblasts (EVT), only Epo, not Epo-R expression was significantly increased in abortive tissue (p=0.006) as well as in hydatidiform mole (p=0.041) in comparison to normal pregnancy. Identification of EVT as Epo-and Epo-R-positive cells was obtained by double immunofluorescence with CK7 and Epo/ Epo-R double staining. Both mole pregnancy and abortion were accompanied by an upregulation of Epo (p=0.041; p=0.018) and Epo-R expression (p=0.007; p=0.015) in decidual tissue as compared to normal pregnancy.

Within our study we were able to demonstrate increased expression of Epo and Epo-R in abortive tissue and hydatidiform mole. Whether upregulation of Epo and Epo-R is secondary to placental hypoxia as part of the abortion process or a risk factor of its own, needs to be further investigated.