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Changes in transcription pattern lead to a marked decrease in COX, CS and SQR activity after the developmental point

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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.

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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.