Erythropoietin and its receptor have been identified in human, murine and o
vine placentas. Based on the common embryonic origin of the placenta and fe
tal membranes, we postulated that erythropoietin is similarly expressed in
the fetal membranes. Using in situ hybridization and immunohistochemistry,
we tested the hypothesis that ovine fetal membranes are sites of erythropoi
etin production and action. At 86, 103 and 138 days gestation, erythropoiet
in mRNA and protein were present in the amnion localized to the cell layer
consisting largely of amniotic epithelium and in the chorion localized to t
he chorionic columnar cells consisting of cytotrophoblasts. Binucleate cell
s, differentiated cytotrophoblasts known to produce hormones, were identifi
ed in the chorion in the region of erythropoietin expression but were not o
bserved in amniotic tissue. The erythropoietin receptor protein was present
in the amnion and chorion at 103 and 138 days gestation but was not observ
ed in either tissue at 86 days. In summary, erythropoietin appears to be pr
oduced as well as utilized within the ovine amnion and chorion. Within the
amnion, the amniotic epithelial cells express the erythropoietin gene where
as, within the chorion, either the cytotrophoblasts or the binuclear cells
may be the source. Due to the presence of the receptor, we speculate that t
he erythropoietin produced in the membranes may mediate fetal membrane func
tion and/or growth through an autocrine and/or paracrine mechanism. Further
, the fetal membranes may be the source of erythropoietin in the amniotic f
luid. (C) 2001 Harcourt Publishers Ltd.