Faculty Collaboration Database

Intrauterine growth retardation alters mitochondrial gene expression and function in fetal and juvenile rat skeletal muscle. Pediatr Res 1998 May;43(5):563-70

Date

05/19/1998

Pubmed ID

9585000

DOI

10.1203/00006450-199805000-00001

Scopus ID

2-s2.0-0031976776 (requires institutional sign-in at Scopus site)   77 Citations

Abstract

Uteroplacental insufficiency alters the anabolic metabolism of the fetus, resulting in intrauterine growth retardation (IUGR). The metabolic and physiologic factors that cause IUGR have long standing consequences after birth. Postnatal growth and glucose metabolism are altered in the IUGR infant. Skeletal muscle is an important component of growth and metabolizes up to 70% of i.v. glucose. The ability of skeletal muscle to metabolize glucose is affected by ATP availability. We hypothesized that gene expression and function of proteins involved in mitochondrial ATP production and distribution would be altered in juvenile IUGR muscle. To test this hypothesis, we used a model of IUGR, induced by bilateral uterine artery ligation in the pregnant rat, that mimics uteroplacental insufficiency in the human. RT-PCR was used to measure the mRNA levels of three important mitochondrial proteins; NADH-ubiquinone-oxireductase subunit 4L(ND-4L), subunit C of the F1F0-ATP synthase (SUC), and adenine nucleotide translocator 1 (ANT1) in IUGR and control rats in fetal and juvenile life. In the fetus, mRNA levels of all three proteins were significantly increased in IUGR skeletal muscle. In contrast, in juvenile animals, mRNA levels of all three proteins were significantly decreased. mRNA levels of other metabolically important proteins, glucose-6-phosphate dehydrogenase and carnitine-palmitoyl-transferase II, were not significantly altered in IUGR juvenile animals. To assess if decreased gene expression is associated with altered mitochondrial function, we measured the mitochondrial NAD+/NADH ratio in d 21 juvenile control and IUGR muscle. At d 21, decreased gene expression if ND-4L, SUC, and ANTI is associated with a decreased mitochondrial NAD+/NADH ratio. The results of our study suggest that the metabolic alterations associated with uteroplacental insufficiency in the rat result in altered fetal and postnatal muscle mitochondrial mRNA expression as well as altered postnatal mitochondrial function.

Author List

Lane RH, Chandorkar AK, Flozak AS, Simmons RA

MESH terms used to index this publication - Major topics in bold

Animals
Carnitine O-Palmitoyltransferase
Electron Transport Complex I
Female
Fetal Growth Retardation
Gene Expression Regulation, Developmental
Glucosephosphate Dehydrogenase
Humans
Mitochondria, Muscle
Mitochondrial ADP, ATP Translocases
Muscle Development
Muscle, Skeletal
NAD
NADH, NADPH Oxidoreductases
Oxidation-Reduction
Placenta
Polymerase Chain Reaction
Pregnancy
Proton-Translocating ATPases
RNA, Messenger
Rats
Rats, Sprague-Dawley
Transcription, Genetic
Uterus