Developmental changes of mitochondrial DNA content and expression of genes involved in mtDNA transcription and maintenance in human fetal liver and muscle tissues

During the process of intra-uterine mammalian fetal development, the oxygen supply in growing fetus is low. A rapid switch from glycolysis-based metabolism to oxidative phosphorylation (OXPHOS) must proceed during early postnatal adaptation to extra-uterine conditions. Mitochondrial biogenesis and mammalian mitochondrial FOF1-ATP synthase assembly (complex V, EC 3.6.3.14, ATPase) are complex processes regulated by multiple transcription regulators and assembly factors. Using RNA expression analysis of rat liver and skeletal tissue (Rattus norvegicus, Berkenhout, 1769), we describe the expression profiles of 20 genes involved in mitochondrial maturation and ATP synthase biogenesis in detail between the 16th and 22nd day of gestation and the first 4 days of life. We observed that the most important expression shift occurred in the liver between the 20th and 22nd day of gestation, indicating that the fetus prepares for birth about two days before parturition. The detailed mechanism regulating the perinatal adaptation process is not yet known. Deeper insights in perinatal physiological development will help to assess mitochondrial dysfunction in the broader context of cell metabolism in preterm newborns or neonates with poor adaptation to extra-uterine life.

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Analysis of Expression Profiles of Genes Involved in FoF1-ATP Synthase Biogenesis During Perinatal Development in Rat Liver and Skeletal Muscle

Spáčilová

Hůlková²,

Hruštincová³

et al. 2016

Physiol Res

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Changes in Transcription Pattern Lead to a Marked Decrease in COX, CS and SQR Activity After the Developmental Point of the 22nd Gestational Week

Kolářová¹,

Křížová²,

Hůlková³

et al. 2018

Physiol Res

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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 22nd 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 13th to 29th 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 22nd GW in comparison with earlier GW. A continuous decline of LH, not correlating with the documented OXPHOS-specific activities, was observed from the 14th to the 24th 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 22nd GW.

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Developmental changes of mitochondrial DNA content and expression of genes involved in mtDNA transcription and maintenance in human fetal liver and muscle tissues

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Analysis of Expression Profiles of Genes Involved in FoF1-ATP Synthase Biogenesis During Perinatal Development in Rat Liver and Skeletal Muscle

Analysis of Expression Profiles of Genes Involved in FoF1-ATP Synthase Biogenesis During Perinatal Development in Rat Liver and Skeletal Muscle

Changes in Transcription Pattern Lead to a Marked Decrease in COX, CS and SQR Activity After the Developmental Point of the 22nd Gestational Week

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