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Fetal Oxygenation from the 23rd to the 36th Week of Gestation Evaluated through the Umbilical Cord Blood Gas Analysis.

ABSTRACT: The embryo and fetus grow in a hypoxic environment. Intrauterine oxygen levels fluctuate throughout the pregnancy, allowing the oxygen to modulate apparently contradictory functions, such as the expansion of stemness but also differentiation. We have recently demonstrated that in the last weeks of pregnancy, oxygenation progressively increases, but the trend of oxygen levels during the previous weeks remains to be clarified. In the present retrospective study, umbilical venous and arterial oxygen levels, fetal oxygen extraction, oxygen content, CO₂, and lactate were evaluated in a cohort of healthy newborns with gestational age < 37 weeks. A progressive decrease in pO₂ levels associated with a concomitant increase in pCO₂ and reduction in pH has been observed starting from the 23rd week until approximately the 33-34th week of gestation. Over this period, despite the increased hypoxemia, oxygen content remains stable thanks to increasing hemoglobin concentration, which allows the fetus to become more hypoxemic but not more hypoxic. Starting from the 33-34th week, fetal oxygenation increases and ideally continues following the trend recently described in term fetuses. The present study confirms that oxygenation during intrauterine life continues to vary even after placenta development, showing a clear biphasic trend. Fetuses, in fact, from mid-gestation to near-term, become progressively more hypoxemic. However, starting from the 33-34th week, oxygenation progressively increases until birth. In this regard, our data suggest that the placenta is the hub that ensures this variable oxygen availability to the fetus, and we speculate that this biphasic trend is functional for the promotion, in specific tissues and at specific times, of stemness and intrauterine differentiation.

SUBMITTER: Filippi L

PROVIDER: S-EPMC10419490 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Fetal Oxygenation from the 23rd to the 36th Week of Gestation Evaluated through the Umbilical Cord Blood Gas Analysis.

Filippi Luca L Pascarella Francesca F Pini Alessandro A Cammalleri Maurizio M Bagnoli Paola P Morganti Riccardo R Innocenti Francesca F Castagnini Nicola N Melosi Alice A Scaramuzzo Rosa Teresa RT

International journal of molecular sciences 20230806 15

The embryo and fetus grow in a hypoxic environment. Intrauterine oxygen levels fluctuate throughout the pregnancy, allowing the oxygen to modulate apparently contradictory functions, such as the expansion of stemness but also differentiation. We have recently demonstrated that in the last weeks of pregnancy, oxygenation progressively increases, but the trend of oxygen levels during the previous weeks remains to be clarified. In the present retrospective study, umbilical venous and arterial oxyge ...[more]

PMID: 37569862

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Project description:IntroductionCerebral white matter injury is the most common neuropathology observed in preterm infants. However, there is increasing evidence that gray matter development also contributes to neurodevelopmental abnormalities. Fetal cerebral ischemia can lead to both neuronal and non-neuronal structural-functional abnormalities, but less is known about the specific effects on interneurons.ObjectiveIn this study we used a well-established animal model of fetal asphyxia in preterm fetal sheep to study neuropathological outcome. We used comprehensive stereological methods to investigate the total number of oligodendrocytes, neurons and somatostatin (STT) positive interneurons as well as 3D morphological analysis of STT cells 14 days following umbilical cord occlusion (UCO) in fetal sheep.Materials and methodsInduction of asphyxia was performed by 25 min of complete UCO in five preterm fetal sheep (98-100 days gestational age). Seven, non-occluded twins served as controls. Quantification of the number of neurons (NeuN), STT interneurons and oligodendrocytes (Olig2, CNPase) was performed on fetal brain regions by applying optical fractionator method. A 3D morphological analysis of STT interneurons was performed using IMARIS software.ResultsThe number of Olig2, NeuN, and STT positive cells were reduced in IGWM, caudate and putamen in UCO animals compared to controls. There were also fewer STT interneurons in the ventral part of the hippocampus, the subiculum and the entorhinal cortex in UCO group, while other parts of cortex were virtually unaffected (p > 0.05). Morphologically, STT positive interneurons showed a markedly immature structure, with shorter dendritic length and fewer dendritic branches in cortex, caudate, putamen, and subiculum in the UCO group compared with control group (p < 0.05).ConclusionThe significant reduction in the total number of neurons and oligodendrocytes in several brain regions confirm previous studies showing susceptibility of both neuronal and non-neuronal cells following fetal asphyxia. However, in the cerebral cortex significant dysmaturation of STT positive neurons occurred in the absence of cell loss. This suggests an abnormal maturation pattern of GABAergic interneurons in the cerebral cortex, which might contribute to neurodevelopmental impairment in preterm infants and could implicate a novel target for neuroprotective therapies.

Project description:BackgroundFetal growth restriction (FGR) is associated with an increased susceptibility for various noncommunicable diseases in adulthood, including cardiovascular and renal disease. During FGR, reduced uteroplacental blood flow, oxygen and nutrient supply to the fetus are hypothesized to detrimentally influence cardiovascular and renal programming. This study examined whether developmental programming profiles, especially related to the cardiovascular and renal system, differ in human umbilical vein endothelial cells (HUVECs) collected from pregnancies complicated by placental insufficiency-induced FGR compared to normal growth pregnancies. Our approach, involving transcriptomic profiling by RNA-sequencing and gene set enrichment analysis focused on cardiovascular and renal gene sets and targeted DNA methylation assays, contributes to the identification of targets underlying long-term cardiovascular and renal diseases.ResultsGene set enrichment analysis showed several downregulated gene sets, most of them involved in immune or inflammatory pathways or cell cycle pathways. seven of the 22 significantly upregulated gene sets related to kidney development and four gene sets involved with cardiovascular health and function were downregulated in FGR (n = 11) versus control (n = 8). Transcriptomic profiling by RNA-sequencing revealed downregulated expression of LGALS1, FPR3 and NRM and upregulation of lincRNA RP5-855F14.1 in FGR compared to controls. DNA methylation was similar for LGALS1 between study groups, but relative hypomethylation of FPR3 and hypermethylation of NRM were present in FGR, especially in male offspring. Absolute differences in methylation were, however, small.ConclusionThis study showed upregulation of gene sets related to renal development in HUVECs collected from pregnancies complicated by FGR compared to control donors. The differentially expressed gene sets related to cardiovascular function and health might be in line with the downregulated expression of NRM and upregulated expression of lincRNA RP5-855F14.1 in FGR samples; NRM is involved in cardiac remodeling, and lincRNAs are correlated with cardiovascular diseases. Future studies should elucidate whether the downregulated LGALS1 and FPR3 expressions in FGR are angiogenesis-modulating regulators leading to placental insufficiency-induced FGR or whether the expression of these genes can be used as a biomarker for increased cardiovascular risk. Altered DNA methylation might partly underlie FPR3 and NRM differential gene expression differences in a sex-dependent manner.

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Fetal Oxygenation from the 23rd to the 36th Week of Gestation Evaluated through the Umbilical Cord Blood Gas Analysis.

Publications

Fetal Oxygenation from the 23rd to the 36th Week of Gestation Evaluated through the Umbilical Cord Blood Gas Analysis.

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