scholarly journals Antenatal PPAR-γ agonist pioglitazone stimulates fetal lung maturation equally in males and females

2020 ◽  
Vol 319 (3) ◽  
pp. L435-L443
Author(s):  
Cindy Lee ◽  
Reiko Sakurai ◽  
Eugene Shin ◽  
Ying Wang ◽  
Jie Liu ◽  
...  
Keyword(s):  
Fetal Lung ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Lung Maturation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alveolar Epithelial ◽  
Ppar Γ ◽  
Antenatal Steroids ◽  
Males And Females ◽  
Fetal Lung Maturation

Antenatal steroids (ANS) accelerate fetal lung maturation and reduce the incidence of respiratory distress syndrome. However, sex specificity, i.e., being less effective in males, and potential long-term neurodevelopmental sequelae, particularly with repeated courses, remain significant limitations. The differential sex response to ANS is likely mediated via the inhibitory effect of fetal androgens on steroid’s stimulatory effect on alveolar epithelial-mesenchymal interactions. Since peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists accelerate lung maturation by stimulating alveolar epithelial-mesenchymal interactions, independent of fetal sex, we hypothesized that the effect of PPAR-γ agonist pioglitazone (PGZ) would be sex-independent. Pregnant Sprague-Dawley rat dams were intraperitoneally administered dexamethasone (DEX) or PGZ on embryonic day (e) 18 and e19. At e20, pups were delivered by cesarean section, and fetal lungs and brains were examined for markers of lung maturation and apoptosis, respectively. Mixed epithelial-fibroblast cell cultures were examined to gain mechanistic insights. Antenatal PGZ increased alveolar epithelial and mesenchymal maturation markers equally in males and females; in contrast, antenatal DEX had sex-specific effects. Additionally, unlike DEX, antenatal PGZ did not increase hippocampal apoptosis. We conclude that PPAR-γ agonist administration is an effective, and probably even a superior, alternative to ANS for accelerating fetal lung maturity equally in both males and females.

SARS-CoV-2: do corticosteroids for fetal lung maturation worsen maternal or fetal outcomes?

2021 ◽  
Vol 29 (2) ◽  
pp. 90-92
Author(s):  
Nashwa Eltaweel ◽  
Samuel Lockley ◽  
Irshad Ahmed ◽  
Bee K Tan
Keyword(s):  
Case Studies ◽  
Clinical Case ◽  
Intraventricular Haemorrhage ◽  
Fetal Lung ◽  
Premature Delivery ◽  
Lung Maturation ◽  
Antenatal Steroids ◽  
Clinical Case Studies ◽  
Inflammatory Processes ◽  
Fetal Lung Maturation

Immune system changes during pregnancy could make pregnant women more susceptible to SARS-Cov-2 infection. The use of corticosteroids within obstetrics has been shown to reduce the risks of respiratory distress syndrome, intraventricular haemorrhage, necrotizing enterocolitis and neonatal death in the baby associated with premature delivery. During the COVID-19 pandemic, corticosteroids have been trialled as a treatment to dampen the ‘cytokine storm’ and associated inflammatory processes. Corticosteroids have long been known to have immunosuppressive effects that could hinder the body's ability to mount a defence against COVID-19 and thereby delaying viral clearance. In this clinical case studies, antenatal steroids for fetal lung maturation appear to be of benefit and did not result in a deterioration of maternal disease. Our clinical case studies support the current recommendations from the Royal College of Obstetricians and Gynaecologists ie corticosteroids for fetal lung maturation is appropriate in patients who are suspected or have confirmed SARS-CoV-2 infection.

Regulation of fetal lung maturation

1990 ◽  
Vol 259 (6) ◽  
pp. L337-L344 ◽  
Author(s):  
I. Gross
Keyword(s):  
Lung Development ◽  
Hormonal Regulation ◽  
Species Differences ◽  
Current Knowledge ◽  
Alveolar Epithelial Cell ◽  
Fetal Lung ◽  
Surfactant Proteins ◽  
Lung Maturation ◽  
Alveolar Epithelial ◽  
Fetal Lung Maturation

The recent identification of the genes for the surfactant proteins has greatly facilitated the study of the regulation of fetal lung alveolar epithelial cell development at the molecular level. In general, expression of the genes for the surfactant proteins is enhanced by the same hormones that stimulate phospholipid synthesis. There are, however, some notable differences that indicate that the genes for the different components of surfactant are independently regulated. Species differences in the response of the surfactant proteins to hormones such as glucocorticoids and adenosine 3',5'-cyclic monophosphate have also been demonstrated. This review focuses on current knowledge of the hormonal regulation of the surfactant proteins against a background of previous studies of lung development.

scholarly journals Histochemical Analyses of Altered Fetal Lung Development Following Single vs Multiple Courses of Antenatal Steroids

2005 ◽  
Vol 53 (12) ◽  
pp. 1469-1479 ◽  
Author(s):  
Zarah J. Pua ◽  
Barbara S. Stonestreet ◽  
Anne Cullen ◽  
Aliakbar Shahsafaei ◽  
Grazyna B. Sadowska ◽  
...  
Keyword(s):  
Cell Injury ◽  
Smooth Muscle Actin ◽  
Fetal Lung ◽  
Nuclear Antigen ◽  
Lung Maturation ◽  
Injury Death ◽  
Fetal Lung Development ◽  
Antenatal Steroids ◽  
Lung Histopathology ◽  
Fetal Lung Maturation

A single course of antenatal steroids is widely used during preterm labor to promote fetal lung maturation. However, little is known regarding efficacy and safety of multiple courses of antenatal steroids. In animal models and clinical trials, treatment with glucocorticoids can inhibit growth. The present study of single- vs multiple-course steroids in pregnant ewes analyzes the effects of steroids vs placebo on fetal lung histopathology. Single-course groups received dexamethasone (Dex) 6 mg or normal saline every 12 hr for 48 hr at 104-106 days of gestation (term = 150 days). Multiple-course groups received the first course at 76-78 days; this was repeated weekly for 5 weeks. At 108 days, lungs were analyzed using immunohistochemistry for α-smooth muscle actin, a myofibroblast marker and proliferating cell nuclear antigen. Cell injury/death was evaluated using TdT-mediated dUTP digoxigenin nick end labeling (TUNEL) analysis. Although fetal growth was restricted by either single or multiple courses of Dex, alveolar development was accelerated as measured by mean linear intercepts. Alveolar walls were thinner, developing septa were longer, and septal myofibroblasts were increased for both Dex groups compared with controls. Cell proliferation increased following multiple steroid courses, especially in the distal parenchyma, with a corresponding decrease in apoptosis. These observations suggest that Dex promotes alveolarization, whether given in single or multiple courses.

scholarly journals Telmisartan prevents the glitazone-induced weight gain without interfering with its insulin-sensitizing properties

2007 ◽  
Vol 293 (1) ◽  
pp. E91-E95 ◽  
Author(s):  
Anne Zanchi ◽  
Abdul G. Dulloo ◽  
Christine Perregaux ◽  
Jean-Pierre Montani ◽  
Michel Burnier
Keyword(s):  
Weight Gain ◽  
Fat Mass ◽  
Zucker Rats ◽  
Peroxisome Proliferator ◽  
Concomitant Treatment ◽  
Sprague Dawley ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Sprague Dawley Rats

Glitazones are peroxisome proliferator-activated receptor (PPAR)-γ agonists with powerful insulin-sensitizing properties. They promote the development of metabolically active adipocytes that can lead to a substantial gain in fat mass. Telmisartan is an ANG II type 1 receptor antagonist with partial PPAR-γ agonistic properties. Recently, telmisartan has been reported to prevent weight gain and improve insulin sensitivity in diet-induced obese rodents. The goal of this study was to examine the influence of telmisartan on pioglitazone-induced weight gain and insulin-sensitizing properties in the following two models of insulin resistance: a nongenetic model (high-fat-fed Sprague Dawley rats) and the genetically obese fa/ fa Zucker rat. After a 4-wk treatment, the pioglitazone-induced increase in fat mass was modest in the Sprague Dawley rats and severe in the Zucker rats. In both models, these effects were substantially decreased by concomitant treatment with telmisartan. The effects of telmisartan on body weight and fat mass in the Zucker rats were abolished by pair feeding, suggesting that it is the result of a decrease in food intake. Telmisartan did not interfere with the insulin-sensitizing properties of pioglitazone. This study demonstrates that telmisartan attenuates the glitazone-induced increase in fat mass without interfering with its insulin-sensitizing properties.

The Effect of Antenatal Steroids on Fetal Lung Maturation between the 34th and 36th Week of Pregnancy

2010 ◽  
Vol 70 (2) ◽  
pp. 95-99 ◽  
Author(s):  
Osman Balci ◽  
Suna Ozdemir ◽  
Alaa S. Mahmoud ◽  
Ali Acar ◽  
Mehmet C. Colakoglu
Keyword(s):  
Fetal Lung ◽  
Lung Maturation ◽  
Antenatal Steroids ◽  
Fetal Lung Maturation

scholarly journals Antenatal steroids for fetal lung maturity: Time to target more frequent doses to fewer women?

2015 ◽  
Vol 8 (4) ◽  
pp. 172-176 ◽  
Author(s):  
Carolyn I Freeman ◽  
Natasha L Hezelgrave ◽  
Andrew H Shennan
Keyword(s):  
High Risk ◽  
Day Treatment ◽  
Fetal Lung ◽  
Optimal Timing ◽  
Antenatal Corticosteroids ◽  
Lung Maturation ◽  
Targeting Therapy ◽  
Antenatal Steroids ◽  
Maximum Benefit ◽  
Fetal Lung Maturation

Antenatal corticosteroids for fetal lung maturation have become mainstay treatment in women thought to be at high-risk of premature birth. To ensure treatment efficacy before delivery, the current practice is to administer steroids early to a woman considered at risk; however, neonatal benefit is lost after the seven-day treatment-to-delivery window. Over half of women who deliver before 34 weeks’ gestation do not receive antenatal corticosteroids within this timeframe, but many still deliver prematurely; however, clinicians are reluctant to administer repeated courses of steroids due to concerns, among others, of impaired fetal growth. However, evidence is mounting regarding the optimal timing for steroids, including substantive benefits close to delivery, and the benefits of repeated courses if delivery has not occurred. Better targeted treatment is required to allow for maximum benefit; reducing unnecessary treatment in low-risk women, while targeting therapy in the high-risk cohort and offering repeat courses if the seven-day window is exceeded. Novel tools to aid prediction may help implement this strategy.

scholarly journals Antenatally administered PPAR-γ agonist rosiglitazone prevents hyperoxia-induced neonatal rat lung injury

2010 ◽  
Vol 299 (5) ◽  
pp. L672-L680 ◽  
Author(s):  
Virender K. Rehan ◽  
Reiko Sakurai ◽  
Julia Corral ◽  
Melissa Krebs ◽  
Basil Ibe ◽  
...  
Keyword(s):  
Lung Injury ◽  
Transforming Growth Factor ◽  
Fetal Lung ◽  
Transforming Growth Factor Β ◽  
Lung Maturation ◽  
Ppar Γ ◽  
Neonatal Lung ◽  
Neonatal Lung Injury ◽  
Fetal Lung Maturation ◽  
Enhancer Factor

The physiological development and homeostasis of the lung alveolus is determined by the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) by the interstitial lipofibroblast. We have recently shown (Dasgupta C et al., Am J Physiol Lung Cell Mol Physiol 296: L1031–L1041, 2009.) that PPAR-γ agonists administered postnatally accelerate lung maturation and prevent hyperoxia-induced lung injury. However, whether the same occurs antenatally is not known. The objective of this study was to test the hypothesis that the potent PPAR-γ agonist rosiglitazone (RGZ), administered antenatally, enhances fetal lung maturation and protects against hyperoxia-induced neonatal lung injury. Sprague-Dawley rat dams were administered either diluent or RGZ (3 mg/kg), at late gestation, to determine its effect on lung maturation and on hyperoxia (95% O2 exposure for 24 h)-induced neonatal lung injury. The lungs were examined for the expression of specific markers of alveolar development (surfactant proteins A and B, cholinephosphate cytidylyltransferase-α, leptin receptor, triglyceride uptake, and [3H]choline incorporation into saturated phosphatidylcholine) and injury/repair, in particular, the markers of transforming growth factor-β signaling (activin receptor-like kinase-5, SMAD3, lymphoid enhancer factor-1, fibronectin, and calponin). Overall, antenatal RGZ accelerated lung maturation and blocked the inhibition of alveolar sacculation and septal wall thinning by hyperoxia. RGZ specifically stimulated the development of the alveolar epithelial type II cell, the lipofibroblast, and the vasculature. The increased expression of the transforming growth factor-β intermediates, such as SMAD3 and lymphoid enhancer factor-1, implicated in hyperoxic lung injury, was also blocked by antenatal RGZ treatment. In conclusion, PPAR-γ agonists can enhance fetal lung maturation and can effectively prevent hyperoxia-induced neonatal lung injury.

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