This study examined levels of erythropoietin (Epo) and soluble Epo receptors (sEpoR) in pregnant women living at high altitudes in Bolivia. Two cohorts were studied: 1) 48 women at low and high altitudes who had blood drawn at three points in pregnancy and 2) 56 women at high altitudes, including those with normal pregnancies and preeclampsia. The study found that healthy women at high altitudes had higher Epo levels during pregnancy compared to sea level controls, likely promoting vascular adaptation. Women who developed preeclampsia had higher sEpoR levels without proportional increases in Epo, suggesting this imbalance may contribute to the vascular dysfunction of preeclampsia

1. Cohort 1 (Longitudinal Study):
48 pregnant women of Andean ancestry residing at low (~300 meters) or high
altitudes (~3600 meters).
These women had whole blood drawn at three points during their pregnancy.
Cohort 2 (Cross-sectional Study):
56 women, all residing at high altitudes, including normotensive or PreE cases
who presented for obstetrical care at 5 hospitals in La Paz-El Alto, Bolivia.
All whole blood draws were taken within 24 hours of admission.
Erythropoietin (Epo) and Soluble Epo Receptors and Their Role in High-Altitude Pregnancy
Gabriel Wolfson1, Enrique Vargas4, Vaughn A. Browne2, Lorna G. Moore3, Colleen G. Julian1
Departments of 1Medicine, 2Emergency Medicine, and 3Obstetrics and Gynecology, UCD-AMC, Aurora, CO;
4Bolivian Institute of High Altitude Biology, La Paz, Bolivia
Introduction:
Preeclampsia (PreE), a common complication of
pregnancy marked by high maternal blood pressure and
protein in the urine, increases the risk of fetal and/or
maternal death. Notably, PreE occurs three times more
often in women living at high altitude (>2500 meters;
8200 feet) compared to sea level. The underlying cause
of PreE is not known, but it is thought that hypoxia, due to
lack of oxygen content or reduced blood flow, causes
abnormal levels of biological factors that influence
vascular function to be released by the mother and/or the
placenta.
Objective:
In this study, we examined whether altitude-related
hypoxic stress leads to changes in maternal blood levels of
two biological factors, erythropoietin (Epo) and its
receptor (sEpoR). Epo is involved in the creation of new
red blood cells, the regulation of vascular function, and
blood vessel growth; sEpoR inhibits the ability of Epo to
perform these biological functions.
Methods
Abstract
Sandwich ELISA (Enzyme Linked Immunosorbent Assay)
[Left to Right] (a) wells in a microtiter plate were covered with a
primary capture antibody with high affinity for Epo or sEpoR; (b)
subject’s blood serum was pipetted into wells and incubated at room
temp. for 2 hours; (c) unbound proteins were washed away and
biotinylated secondary antibodies specific to Epo or sEpoR were
added to well and incubated for 2 hours at room temp; (d)
Streptavidin conjugated to horseradish peroxidase (HRP) was added
to bind with very high affinity to biotinylated secondary antibodies;
(e) HRP catalyzed the breakdown of TMB, a peroxide solution, leading
to a visible colorimetric change; (f) [not depicted] target protein
concentrations were determined by absorbance spectroscopy in
relationship to color change.
Discussion
(Image courtesy of Epitomics)
Our data show that healthy, pregnant women living at HA
(~11,800 feet) had higher Epo levels relative to SL controls
without any change in sEpoR; we expect that this response
promotes vascular adaptation to pregnancy and enhances
blood flow to the placenta and fetus.
In addition, we found that women who develop PreE during
their pregnancy had higher levels of sEpoR without a
proportional increase in Epo. We speculate higher sEpoR in
PreE may contribute to the vascular dysfunction hallmark to
the condition.
Acknowledgements
Very Special Thanks to:
Colleen Julian, PhD
Lorna Moore, PhD
David Schwartz, MD
Ivana Yang, PhD
This Research Is funded by NIH grant HL079647 and NIH
Building Interdisciplinary Research Careers Women's Health
grant 5K12 HD057022-07
Subjects
Not
pregnant
20
weeks
36
weeks
40
weeks
(full term)
Results
(A and B) Concentrations of Epo and sEpoR in blood serum drawn from patients at two
elevations: high altitudes (HA) and sea level (SL); from three time points: not pregnant (NP)
and after 20 and 36 weeks into pregnancy.
• Epo levels were greater at HA than SL during pregnancy, but equivalent in the non-
pregnant state.
• In contrast, sEpoR levels were unchanged by pregnancy or HA.
A B
(C and D) Hemoglobin and hematocrit levels, a measure of red blood cell concentrations and
the percentage of whole blood volume comprised of red blood cells, respectively, in whole
blood drawn from patients at two elevations: high altitudes (HA) and sea level (SL); from
three time points: not pregnant (NP) and after 20 and 36 weeks into pregnancy.
• As expected, hemoglobin and hematocrit levels were greater at high altitude during
pregnancy as well as in the non-pregnant state.
• Hemoglobin and hematocrit fall during pregnancy; our data demonstrate that the decline
in hemoglobin and hematocrit during pregnancy is equivalent between HA and SL.
C D
(E, F, and G) Concentrations of Epo, sEpoR, and hemoglobin in blood serum
or whole blood drawn from patients who had a normotensive pregnancy
(Norm; 31.5 weeks) and patients who developed PreE (34.4 weeks).
(Figures courtesy of Colleen Julian)
E F
G
Results (continued)
(a) (b) (c) (d) (e)