Uteroplacental insufficiency alters cerebral mitochondrial gene expression and DNA in fetal and juvenile rats.
Uteroplacental insufficiency increases the risk of perinatal and long-term neurologic morbidity by depriving the fetus of oxidative substrate and causing intrauterine growth retardation. Skeletal muscle and liver from growth retarded fetal and juvenile rats respond to this deprivation by altering mitochondrial gene expression and function. The objective of this study was to determine whether cerebral mitochondrial mRNA is similarly altered in fetal and juvenile growth retarded rats and to correlate these alterations with mitochondrial DNA and marker protein levels. To fulfill this objective, mRNA levels of four important mitochondrial proteins were quantified using RT-PCR in growth retarded and sham-operated control fetal and juvenile rat brains; these proteins were NADH-ubiquinone oxireductase subunit 4, subunit C of the F1F0-ATPase, and the adenine nucleotide transporters 1 and 2. Mitochondrial DNA/nuclear DNA ratios and mitochondrial 60 kD marker protein levels were also quantified in growth retarded and sham-operated control fetal and juvenile rat brains using PCR and Western Blotting, respectively. Cerebral mRNA levels of all four proteins were increased in the IUGR fetuses and decreased in the IUGR juvenile animals. Cerebral mitochondrial/nuclear DNA ratios and mitochondrial marker protein levels were not significantly altered in the IUGR fetuses; however, both were significantly diminished in IUGR juvenile pups. These studies suggest that the metabolic stresses associated with uteroplacental insufficiency in the rat cause altered fetal and postnatal cerebral mitochondrial mRNA and DNA levels.
Lane
R H
RH
Department of Pediatrics, University of California-Los Angeles, School of Medicine, Mattel Children's Hospital, UCLA, 90095, USA.
Tsirka
A E
AE
Gruetzmacher
E M
EM
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation; D020869:Gene Expression Profiling; D008928:Mitochondria / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D021041:Placental Circulation / Q000235:genetics*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D004272:DNA, Mitochondrial; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger