Developmental response to hypoxia.
Molecular mechanisms underlying fetal growth restriction due to placental insufficiency and in utero hypoxia are not well understood. In the current study, time-dependent (3 h-11 days) changes in fetal tissue gene expression in a rat model of in utero hypoxia compared with normoxic controls were investigated as an initial approach to understand molecular events underlying fetal development in response to hypoxia. Under hypoxic conditions, litter size was reduced and IGFBP-1 was up-regulated in maternal serum and in fetal liver and heart. Tissue-specific, distinct regulatory patterns of gene expression were observed under acute vs. chronic hypoxic conditions. Induction of glycolytic enzymes was an early event in response to hypoxia during organ development; consistently, tissue-specific induction of calcium homeostasis-related genes and suppression of growth-related genes were observed, suggesting mechanisms underlying hypoxia-related fetal growth restriction. Furthermore, induction of inflammation-related genes in placentas exposed to long-term hypoxia (11 days) suggests a mechanism for placental dysfunction and impaired pregnancy outcome accompanying in utero hypoxia.
Huang
S-T Joseph
ST
Department of Obstetrics and Gynecology, Stanford University Medical Center, California 94305-5317, USA.
Vo
Kim Chi T
KC
Lyell
Deirdre J
DJ
Faessen
Gerarda H
GH
Tulac
Suzana
S
Tibshirani
R
R
Giaccia
Amato J
AJ
Giudice
Linda C
LC
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism; D005333:Fetus / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006019:Glycolysis; D006706:Homeostasis; D000860:Hypoxia / Q000235:genetics* / Q000503:physiopathology*; D007249:Inflammation / Q000235:genetics; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D008098:Litter Size; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D010927:Placental Insufficiency / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011256:Pregnancy Outcome; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D018970:Insulin-Like Growth Factor Binding Protein 1; D012333:RNA, Messenger; D002118:Calcium