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Changes in transcription pattern lead to a marked decrease in COX, CS and SQR activity after the developmental point
H Kolarova1, J Krizova, M Hulkova
1Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. marketa.tesarova@lf1.cuni.cz.
Abstract:
Tissue differentiation and proliferation throughout fetal development interconnect with changes in the oxidative phosphorylation system (OXPHOS) on the cellular level. Reevaluation of the expression data revealed a significant increase in COX4 and MTATP6 liver transcription levels after the 22(nd) gestational week (GW) which inspired us to characterize its functional impact. Specific activities of cytochrome c oxidase (COX), citrate synthase (CS), succinate-coenzyme Q reductase (SQR) and mtDNA determined by spectrophotometry and RT-PCR were studied in a set of 25 liver and 18 skeletal muscle samples at 13(th) to 29(th) GW. Additionally, liver hematopoiesis (LH) was surveyed by light microscopy. The mtDNA content positively correlated with the gestational age only in the liver. The activities of COX, CS and SQR in both liver and muscle isolated mitochondria significantly decreased after the 22(nd) GW in comparison with earlier GW. A continuous decline of LH, not correlating with the documented OXPHOS-specific activities, was observed from the 14(th) to the 24(th) GW indicating their exclusive reflection of liver tissue processes. Two apparently contradictory processes of increasing mtDNA transcription and decreasing OXPHOS-specific activities seem to be indispensable for rapid postnatal adaptation to high energy demands. The inadequate capacity of mitochondrial energy production may be an important factor in the mortality of children born before the critical developmental point of the 22(nd) GW.
Insights
Fetal liver and muscle tissue show decreasing oxidative phosphorylation (OXPHOS) enzyme activity after 22 weeks gestation, despite rising mitochondrial DNA transcription. This may impact infant survival.
Area of Science:
- Biochemistry
- Developmental Biology
- Cellular Respiration
Background:
- Fetal development involves complex cellular changes, including shifts in oxidative phosphorylation (OXPHOS).
- Previous data indicated increased COX4 and MTATP6 liver transcription after 22 weeks gestational age (GW).
Purpose of the Study:
- To investigate the functional impact of observed changes in OXPHOS gene expression during fetal development.
- To analyze specific OXPHOS enzyme activities and mitochondrial DNA (mtDNA) content in fetal liver and skeletal muscle.
Main Methods:
- Spectrophotometry and RT-PCR were used to measure COX, CS, SQR activities, and mtDNA content.
- Liver and skeletal muscle samples from 13-29 GW were analyzed.
- Liver hematopoiesis (LH) was assessed via light microscopy.
Main Results:
- mtDNA content correlated with gestational age in the liver only.
- COX, CS, and SQR activities significantly decreased in both liver and muscle mitochondria after 22 GW.
- Liver hematopoiesis declined from 14-24 GW, independent of OXPHOS activity.
Conclusions:
- Decreasing OXPHOS activity alongside increasing mtDNA transcription appears crucial for neonatal adaptation.
- Impaired mitochondrial energy production capacity may contribute to mortality in infants born before 22 GW.
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