|My research centers on the physiological
mechanisms underlying the normal maternal physiological responses to pregnancy
and the pregnancy complications of fetal growth restriction and preeclampsia. I use the chronic hypoxia of residence at high
altitude (>2500 m or 8000 ft) as a natural laboratory for studying these mechanisms
since high altitude
exerts one of the strongest influences on fetal growth (being second in
magnitude only to gestational age) and triples the frequency of preeclampsia. With students, fellows and faculty colleagues
from obstetrics & gynecology and other disciplines (anesthesiology,
anthropology, cancer biology, genetics, medicine, pediatrics, physiology, and
public health) and the aid of NIH, NSF or other federal funding, we have
published more than 200 articles documenting the effects of chronic hypoxia on
maternal and fetal well being. In
particular our human studies have shown that altitude lowers birth weight an
average of 102 g/1000 m and is associated with less pregnancy-associated rise
in uterine artery blood flow, due in turn to smaller uterine artery diameters. Experimental animal studies have shown that
chronic hypoxia vs. normoxia reduces uterine artery nitric oxide production,
vasodilator response to flow, growth and remodeling, suggesting that chronic
hypoxia interferes with the normal maternal uterine vascular responses to
pregnancy. Multigenerational populations
(Andeans, Tibetans) are largely protected from hypoxia-associated fetal growth
restriction, due in part to being able to attain greater uterine artery diameter
and blood flow than shorter-term residents (Europeans, Chinese). Our recent whole-genome scan and gene-expression
studies have identified several genes likely involved. Current work is aimed at identifying the
specific gene variants and physiological mechanisms by which they exert their
effects with hopes that such studies will aid not only in understanding
processes of evolutionary adaptation but also our ability to identify persons
at risk for pregnancy complications and/or design more effective therapies for
their treatment or prevention.
Key publications include:
AW, Mao X, Akey JM, Bauchet M, Brutsaert T, Mei R, Pinto D, Scherer S, Parra
EJ, Julian CG, Wilson MJ, Moore LG, Shriver MD. Identifying signatures of
natural selection in Tibetan and Andean populations using dense genome scan
data. Plos Genetics, Sept 2010; 6(9): 1-14.
CG, Galan HL, Wilson M, Desilva W, Cioffi-Ragan D, Schwartz J, Moore LG.
Lower uterine artery blood flow and higher endothelin relative to nitric
oxide metabolite levels are associated with reductions in birth weight at high
altitude. Am J Physiol Regul Integr Comp Physiol. 2008; Sep 295(3):
- Julian CG, Vargas E,
MacCannell W, Armaza JF, Niermeyer S, Moore, LG. High-altitude ancestry
protects against hypoxia-associated reductions in birth weight. Arch Dis Child Fetal Neonatal Ed 2007; Sep 92(5): F372-377.
- Mateev S, Sillau AH, Mouser R, McCullough RE, White MM, Young DY, Moore
LG. Chronic hypoxia opposes
pregnancy-induced increase in uterine artery vasodilator response to flow. Am J Physiol 2003; 284:H820-H829.
- Keyes LE, Armaza JF, Niermeyer S, Vargas E, Young DY, Moore
LG. Intrauterine growth restriction, preeclampsia and intrauterine mortality at
high altitude in Bolivia. Pediatr Res.
2003; Jul 54(1): 20-25.
- Moore LG, Young D, McCullough RE,
Droma T, Zamudio S. Tibetan protection
from intrauterine growth restriction (IUGR) and reproductive loss at high
altitude. Am J Hum Biol 2001; 13(5):
- White MM, McCullough RE, Dyckes R,
Robertson AD, Moore LG. Chronic hypoxia,
pregnancy, and endothelium-mediated relaxation in guinea pig uterine and
thoracic arteries. Am J Physiol 2000; 278(6): H2069-H2075.
- Jensen GM, Moore LG. The effect of high altitude and other risk
factors on birth weight: independent or interactive? Am J Public Health 1997;
- Niermeyer S, Yang P, Shanmina,
Drolkar, Zhuang J, Moore LG. Arterial oxygen saturation in Tibetan and Han
infants born in Lhasa, Tibet. N Engl J
Med 1995; 333(19): 1248-1252.
- Palmer SK, Zamudio S, Coffin C,
Parker S, Stamm E, Moore LG. Quantitative estimation of human uterine artery
blood flow and pelvic blood flow redistribution in pregnancy. Obstet Gynecol 1992;