Biology Reference
In-Depth Information
found intact in the plasma, and another 8-10% reached the bone marrow
[131].
Current research focuses on the clinical effects of rEPO on the developing
gastrointestinal tract. A retrospective study in preterm neonates (body
weight < 1,250 g; n = 260), who received rEPO to prevent anemia of prematu-
rity, showed a lower incidence of stage II and III necrotizing enterocolitis
(4.6%
versus
10.8%) compared with controls (n = 223) [135]. Feeding intol-
erance is a common problem in neonatal intensive care among ill preterm
babies and may lead to intestinal villous atrophy of a result of being
nihil per
os
during parenteral feeding. Recent studies investigate the effects of the appli-
cation of a simulated amniotic fluid which contains rEPO beside recombinant
G-GSF, on the maturation and repair of the epithelial of the gastrointestinal
tract [136, 137].
Female reproductive organs
Uterus and oviduct
In the murine uterus, EPO and EPOR mRNA are expressed, and EPO protein
is produced
in vitro
and
in vivo
in an estrogen-dependent manner. EPO mRNA
levels increase one hour after estrogen administration, reach a peak after four
hours, but decrease after eight hours [138]. Interestingly, this decrease is not
the loss of responsiveness of the uterine EPO-producing cells to estrogen
[139].
EPO
gene expression in the uterus in response to hypoxia also needs the
presence of estrogen which indicates a unique regulation of the
EPO
gene.
In
vivo
experiments showed that endogenous or recombinant EPO induces uter-
ine hypertrophy and endometrial growth [138]. Immunohistochemistry reveals
EPOR expression in uterine microvascular endothelial cells, but changes in its
expression level are not reported [138]. The down-regulation of the respon-
siveness to estrogen in uterine EPO-producing cells may be very important to
prevent uterine angiogenesis in an estrogen cycle stage where it should not
occur [139].
In human uterine tissue specimens of fertile, premenopausal women, EPO
and EPOR are expressed in isolated epithelial, but not stroma cells [140].
During menstrual cycle, EPO expression in these cells is cycledependent and
higher during the secretory phase than in the proliferative phase. As shown by
immunohistochemistry, EPO and EPOR protein expression in glandular
epithelial cells is increased during the mid-proliferative phase and maintained
during the late proliferative phase and the secretory phases [140]. These data
suggests that also in humans ovarian steroids may stimulate EPO production
in human endometrial glandular epithelial cells.
Ovary and oviduct
EPO is also expressed in the mammalian ovary and oviduct [141]. In contrast
to the uterus,
EPO
gene expression in the murine oviduct can be induced by
