Biology Reference
In-Depth Information
hypoxia in the absence of estrogen, although in general EPO mRNA in the
oviduct is also inducible by estrogen [141]. EPOR biology and implication of
EPO expression in the oviduct are unknown.
Placenta
Expression of
EPO
and
EPOR
genes has been described in the placenta of
humans, mice, rats, and sheep [142-146]. The expression of
EPOR
gene in
human placental tissue and trophoblast-derived choricarcinoma Jar cells has
been detected by RT-PCR [144, 145]. Using immunohistochemistry, EPOR
expression has been identified in the villous and extravillous cytotrophoblast
cells as well as in the syncytiotrophoblast of the human placenta at all gesta-
tional stages [145]. EPOR is expressed by cells within the villous core, includ-
ing endothelial cells of feto-placental blood vessels [145]. The presence of
EPOR protein and its phosphorylation in response to rEPO application in tro-
phoblasts has been confirmed by Western blot analysis [145].
The function of EPO in the placenta is not totally understood. The macro-
scopic examination of the placenta in mice with heterozygous maternal and
homozygous fetal deletion of
EPO
or
EPOR
gene has been unrevealing. The
finding of EPO mRNA, protein, and EPOR localized to the fetal-maternal
interface within the cotyledon in a region populated with binucleate cells, sug-
gests that EPO may potentially mediate cellular function in both the maternal
and the fetal portions of the placenta [146]. Based on these data, an autocrine
role for EPO in the survival, proliferation, or differentiation of placental tro-
phoblasts or in angiogenesis is proposed.
EPO and EPOR are expressed in ovine membranes, where EPO may medi-
ate the development and/or function of the amnion and chorion [147]. EPO
mRNA expression was detected in both the amnion (amniotic epithelium) and
the chorion (chorionic cytotrophoblasts), but was absent from the connective
tissue layer (extracellular matrix) between the amnion and chorion [147]. The
EPO protein is localized exactly at the same sites. EPOR expression shows a
developmental expression pattern. While EPOR is not detectable in the mem-
branes early in gestation, it is found late in gestation both in the amniotic
epithelium and chorionic cytotrophoblasts [147]. Further studies are necessary
to determine the function of EPO in fetal membranes.
Mammary gland
Conflicting data are reported regarding whether EPO is expressed in the
mature, non-lactating breast of non-pregnant women [127, 148]. However,
EPO immunoreactivity in mammary tubular epithelial cells increases during
pregnancy, and robust EPO production is obvious during lactation [127]. EPO
concentrations in human milk increase during the lactating period,with high-
est levels after the day 50
post partum
. EPO concentrations do not differ in
fore, mid, or hind milk [127]. EPO concentrations in milk are higher in moth-
ers who were smokers or who had significant peripartum anemia [125].
Furthermore, EPO concentrations in milk and plasma increase during subcu-
