Altered purine and pentose phosphate pathway metabolism in uteroplacental insufficiency-induced intrauterine growth restriction offspring rats impair intestinal function.

This study aimed to identify metabolic alterations in the small intestine of newborn rats with intrauterine growth restriction (IUGR), a condition linked to intestinal dysfunction. Pregnant Sprague Dawley rats underwent bilateral uterine artery ligation on gestational day 17 to induce intrauterine growth restriction or sham surgery. Rat pups were delivered spontaneously on gestational day 22. Small intestine tissues were collected on postnatal days 0 and 7 from offspring. Liquid chromatography-mass spectrometry analysis was performed to investigate untargeted metabolomic profiles. Western blot analysis assessed protein expression of key regulators. Newborn rats with intrauterine growth restriction exhibited distinct small intestine metabolic profiles compared to controls on postnatal day 0. Notably, significant alterations were observed in purine metabolism, the pentose phosphate pathway, and related pathways. Western blot analysis revealed a decrease expression in transketolase, a key enzyme of the pentose phosphate pathway, suggesting impaired activity of the pentose phosphate pathway. Additionally, decreased expression of tight junction proteins ZO-1 and occludin indicated compromised intestinal barrier function in rats with intrauterine growth restriction. Similar metabolic disruptions persisted on postnatal day 7, with further reductions in tricarboxylic acid cycle intermediates and folate biosynthesis precursors. Interestingly, lysyl-glycine, a protein synthesis marker, was elevated in rats with intrauterine growth restriction. Our findings reveal a distinct metabolic signature in the small intestine of neonatal rats with intrauterine growth restriction, characterized by disruptions in the pentose phosphate pathway, purine metabolism, and energy production pathways. These novel insights suggest potential mechanisms underlying IUGR-associated intestinal dysfunction and impaired growth.

Uteroplacental insufficiency decreases leptin expression and impairs lung development in growth-restricted newborn rats.

BACKGROUND: The study aimed to analyze the effect of uteroplacental insufficiency (UPI) on leptin expression and lung development of intrauterine growth restriction (IUGR) rats. METHODS: On day 17 of pregnancy, time-dated Sprague-Dawley rats were randomly divided into either an IUGR group or a control group. Uteroplacental insufficiency surgery (IUGR) and sham surgery (control) were conducted. Offspring rats were spontaneously delivered on day 22 of pregnancy. On postnatal days 0 and 7, rats' pups were selected at random from the control and IUGR groups. Blood was withdrawn from the heart to determine leptin levels. The right lung was obtained for leptin and leptin receptor levels, immunohistochemistry, proliferating cell nuclear antigen (PCNA), western blot, and metabolomic analyses. RESULTS: UPI-induced IUGR decreased leptin expression and impaired lung development, causing decreased surface area and volume in offspring. This results in lower body weight, decreased serum leptin levels, lung leptin and leptin receptor levels, alveolar space, PCNA, and increased alveolar wall volume fraction in IUGR offspring rats. The IUGR group found significant relationships between serum leptin, radial alveolar count, von Willebrand Factor, and metabolites. CONCLUSION: Leptin may contribute to UPI-induced lung development during the postnatal period, suggesting supplementation as a potential treatment. IMPACT: The neonatal rats with intrauterine growth restriction (IUGR) caused by uteroplacental insufficiency (UPI) showed decreased leptin expression and impaired lung development. UPI-induced IUGR significantly decreased surface area and volume in lung offspring. This is a novel study that investigates leptin expression and lung development in neonatal rats with IUGR caused by UPI. If our findings translate to IUGR infants, leptin may contribute to UPI-induced lung development during the postnatal period, suggesting supplementation as a potential treatment.

Intrauterine growth restriction alters kidney metabolism at the end of nephrogenesis.

BACKGROUND: This study investigated the effect of uteroplacental insufficiency (UPI) on renal development by detecting metabolic alterations in the kidneys of rats with intrauterine growth restriction (IUGR). METHODS: On gestational day 17, pregnant Sprague Dawley rats were selected and allocated randomly to either the IUGR group or the control group. The IUGR group received a protocol involving the closure of bilateral uterine vessels, while the control group underwent a sham surgery. The rat pups were delivered on gestational day 22 by natural means. Pups were randomly recruited from both the control and IUGR groups on the seventh day after birth. The kidneys were surgically removed to conduct Western blot and metabolomic analyses. RESULTS: IUGR was produced by UPI, as evidenced by the significantly lower body weights of the pups with IUGR compared to the control pups on postnatal day 7. UPI significantly increased the levels of cleaved caspase-3 (p < 0.05) and BAX/Bcl-2 (p < 0.01) in the pups with IUGR. Ten metabolites exhibited statistically significant differences between the groups (q < 0.05). Metabolic pathway enrichment analysis demonstrated statistically significant variations between the groups in the metabolism related to fructose and mannose, amino and nucleotide sugars, and inositol phosphate. CONCLUSIONS: UPI alters kidney metabolism in growth-restricted newborn rats and induces renal apoptosis. The results of our study have the potential to provide new insights into biomarkers and metabolic pathways that are involved in the kidney changes generated by IUGR.

Effects of uteroplacental insufficiency on growth-restricted rats with altered lung development: A metabolomic analysis.

Background: Intrauterine growth restriction (IUGR) is among the most challenging problems in antenatal care. Several factors implicated in the pathophysiology of IUGR have been identified. We aimed to investigate the effect of UPI on lung development by identifying metabolic changes during the first seven days of postnatal life. Materials and methods: On gestation day 17, four time-dated pregnant Sprague Dawley rats were randomized to a IUGR group or a control group, which underwent an IUGR protocol comprising bilateral uterine vessel ligation and sham surgery, respectively. On gestation day 22, 39 control and 26 IUGR pups were naturally delivered. The rat pups were randomly selected from the control and IUGR group on postnatal day 7. The pups' lungs were excised for histological, Western blot, and metabolomic analyses. Liquid chromatography mass spectrometry was performed for metabolomic analyses. Results: UPI induced IUGR, as evidenced by the IUGR rat pups having a significantly lower average body weight than the control rat pups on postnatal day 7. The control rats exhibited healthy endothelial cell healthy and vascular development, and the IUGR rats had a significantly lower average radial alveolar count than the control rats. The mean birth weight of the 26 IUGR rats (5.89 ± 0.74 g) was significantly lower than that of the 39 control rats (6.36 ± 0.55 g; p < 0.01). UPI decreased the levels of platelet-derived growth factor-A (PDGF-A) and PDGF-B in the IUGR newborn rats. One-way analysis of variance revealed 345 features in the pathway, 14 of which were significant. Regarding major differential metabolites, 10 of the 65 metabolites examined differed significantly between the groups (p < 0.05). Metabolite pathway enrichment analysis revealed significant between-group differences in the metabolism of glutathione, arginine-proline, thiamine, taurine-hypotaurine, pantothenate, alanine-aspartate-glutamate, cysteine-methionine, glycine-serine-threonine, glycerophospholipid, and purine as well as in the biosynthesis of aminoacyl-tRNA, pantothenate, and CoA. Conclusions: UPI alters lung development and metabolomics in growth-restricted newborn rats. Our findings may elucidate new metabolic mechanisms underlying IUGR-induced altered lung development and serve as a reference for the development of prevention and treatment strategies for IUGR-induced altered lung development.

Association between clinical, laboratory findings and chest CT in COVID-19 in a secondary hospital in Jakarta, Indonesia.

INTRODUCTION: A new emerging infectious disease caused by SARS-CoV-2 has caused a global pandemic. Early diagnosis is essential to prevent and halt the spread of the disease, patient management and isolation. In this study, we aimed to reveal correlations between clinical and laboratory findings with chest CT. METHODS: This in an observational case series single center study in a secondary hospital in Jakarta, Indonesia. Patients were included if they had typical symptoms and positive RT-PCR for SARS-CoV-2. RESULTS: Forty-two patients with positive RT-PCR were included in this study. Typical CT findings were present in 33 (78.6%). We found a positive correlation between patients in whom the imaging was performed after the 4th day of symptoms and chest CT findings (r=0.365 p<0.05). In receiver operating characteristic analysis of this parameter, the area under curve (AUC) was 0.678, and the sensitivity and specificity were 0.96 and 0.44, respectively. CONCLUSIONS: Early diagnosis of COVID-19 is essential to promptly isolate and treat suspected patients. Utilization of chest CT to help diagnosis in this pandemic era needs to be considered by healthcare facilities especially if RT-PCR is limited.