Chronic hypoxia differentially increases glutathione content and gamma-glutamyl cysteine synthetase expression in fetal guinea pig organs.
OBJECTIVE
Glutathione is a natural antioxidant in the fetus and adult. We sought to determine whether maternal hypoxia alters glutathione levels in fetal organs as an adaptive response to the reduced oxygenation.


METHODS
Timed pregnant guinea pigs were housed in either a Plexiglas chamber containing 10.5% O(2) from 46 to 60 days gestation (HPX, n=6) or in room air, as the normoxic control (NMX, n=5). Pregnant guinea pigs were anesthetized at near term ( approximately 60 days, term=65 days) and liver, lungand kidney were excised from anesthetized fetuses and stored frozen (-80 degrees C) prior to sample processing. Using the hypoxia marker, pimonidazole, we measured a hypoxia-induced increase in stained cells of fetal liver compared to no change in either the lung or kidney. To measure the effect of hypoxia among different organs, total glutathione (GSH) content and protein levels of gamma-glutamyl cysteine synthetase (gamma-GCS) were measured from the same organs.


RESULTS
Maternal hypoxia increased (P<0.05) total glutathione levels by 121% in the fetal liver but had no effect in either fetal lung or kidney. Chronic hypoxia increased (P<0.05) gamma-GCS protein levels in all three fetal organs studied.


CONCLUSIONS
These results demonstrate that the fetal response to maternal hypoxia may be organ specific. The increase in fetal liver glutathione via upregulation of gamma-GCS may be an important adaptive response to prolonged hypoxic stress.
Oh
Chien
C
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Dong
Yafeng
Y
Harman
Christopher
C
Mighty
Hugh E
HE
Kopelman
Jerome
J
Thompson
Loren P
LP
D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D005260:Female; D005311:Fetal Hypoxia / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D005333:Fetus; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis*; D005978:Glutathione / Q000378:metabolism*; D006168:Guinea Pigs; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000196:embryology / Q000201:enzymology / Q000378:metabolism*; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D009929:Organ Size / Q000502:physiology; D011247:Pregnancy; D019289:Pyruvic Acid / Q000097:blood
D019344:Lactic Acid; D019289:Pyruvic Acid; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione