Asthma Pregnancy Alters Postnatal Development of Chromaffin Cells in the Rat Adrenal Medulla

Wu, Xiuming; Li, Xiaozhao; Zou, Ye-Qiang; Zou, Jun-Tao; Li, Yuanyuan; Feng, Juntao

doi:10.1371/journal.pone.0020337

Cited by 7 publications

(20 citation statements)

References 33 publications

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“…This result suggested that asthma can affect the development of the adrenal medulla in utero [10]. Interestingly, our recent results also showed that when these offspring rats matured, their susceptibility to OVA-induced asthma was increased due to the dysfunctional adrenal medulla (unpublished data).…”

Section: Introductionmentioning

confidence: 64%

“…Furthermore, our recent study indicated that asthma during rodent pregnancy was able to promote AMCCs to differentiate into neurons in the offspring rat pups and inhibited their ability to synthesize EPI. This result suggested that asthma can affect the development of the adrenal medulla in utero [10] . Interestingly, our recent results also showed that when these offspring rats matured, their susceptibility to OVA-induced asthma was increased due to the dysfunctional adrenal medulla (unpublished data).…”

Section: Introductionmentioning

confidence: 91%

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The Effect of Unilateral Adrenalectomy on Transformation of Adrenal Medullary Chromaffin Cells In Vivo: A Potential Mechanism of Asthma Pathogenesis

Zou

Feng

2012

PLoS ONE

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BackgroundDecreased epinephrine (EPI) is an important underlying factor of bronchoconstriction in asthma. Exogenous β2-adrenergic receptor agonist is one of the preferred options to treat asthma. We previously showed that this phenomenon involved adrenal medullary chromaffin cell (AMCC) transformation to a neuron phenotype. However, the underlying molecular mechanism is not fully understood. To further explore this, an asthmatic model with unilateral adrenalectomy was established in this study.Methodology/Principal FindingsThirty-two rats were randomly into four groups (n = 8 each) control rats (controls), unilateral adrenalectomy rats (surgery-control, s-control), asthmatic rats (asthma), unilateral adrenalectomy asthmatic rats (surgery-induced asthma, s-asthma). Asthmatic rats and s-asthmatic rats were sensitized and challenged with ovalbumin (OVA). The pathological changes in adrenal medulla tissues were observed under microscopy. EPI and its rate-limiting enzyme, phenylethanolamine N-methyl transferase (PNMT), were measured. Peripherin, a type III intermediate filament protein, was also detected in each group. The asthmatic rats presented with decreased chromaffin granules and swollen mitochondria in AMCCs, and the s-asthmatic rats presented more serious pathological changes than those in asthmatic rats and s-control rats. The expressions of EPI and PNMT in asthmatic rats were significantly decreased, as compared with levels in controls (P<0.05), and a further decline was observed in s-asthmatic rats (P<0.05). The expression of peripherin was higher in the asthmatic rats than in the controls, and the highest level was found in the s-asthmatic rats (P<0.05).Conclusion/SignificanceCompared with asthmatic rats and s-control rats, the transformation tendency of AMCCs to neurons is more obvious in the s-asthmatic rats. Moreover, this phenotype alteration in the asthmatic rats is accompanied by reduced EPI and PNMT, and increased peripherin expression. This result provides further evidence to support the notion that phenotype alteration of AMCCs contributes to asthma pathogenesis.

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Section: Introductionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 91%

The Effect of Unilateral Adrenalectomy on Transformation of Adrenal Medullary Chromaffin Cells In Vivo: A Potential Mechanism of Asthma Pathogenesis

Zou

Feng

2012

PLoS ONE

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“…Bronchoalveolar lavage fluid (BALF) was centrifuged at 1,000 rpm for 10 min at 4°C. The sediment was then stained with May-Grunwald-Giemsa and a total of 300 cells were counted (33).…”

Section: Methodsmentioning

confidence: 99%

“…In contrast, MoTr could upregulate EPI and CORT levels. This could explain the occurrence of airway hyperresponsiveness among endurance athletes after competitions because the blunted sympathoadrenal system is unable to release sufficient EPI to dilate the bronchus (12,16,33) after prolonged high-intensity training. The time required for rats to reach exhaustion was used to evaluate the efficacy of different training regimens in inducing exercise tolerance.…”

Section: L608 Adrenal Medulla Cells Conversion In Eibmentioning

confidence: 99%

High-intensity training induces EIB in rats through neuron transdifferentiation of adrenal medulla chromaffin cells

Feng

Xun

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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He R, Feng J, Xun Q, Qin Q, Hu C. High-intensity training induces EIB in rats through neuron transdifferentiation of adrenal medulla chromaffin cells. Am J Physiol Lung Cell Mol Physiol 304: L602-L612, 2013. First published February 15, 2013 doi:10.1152/ajplung.00406.2012.-A high prevalence of exercise-induced bronchoconstriction (EIB) can be found in elite athletes, but the underlying mechanisms remain elusive. Airway responsiveness, NGF and epinephrine (EPI) levels, and chromaffin cell structure in high-(HiTr) and moderate-intensity training (MoTr) rats with or without ovalbumin (OVA) sensitization were measured in a total of 120 male Sprague-Dawley rats. The expression of NGF-associated genes in rat adrenal medulla was tested. Both HiTr and OVA intervention significantly increased airway resistance to aerosolized methacholine measured by whole body plethysmography. HiTr significantly increased inflammatory reaction in the lung with a major increase in peribronchial lymphocyte infiltration, whereas OVA significantly increased the infiltration of various inflammatory cells with an over 10-fold increase in eosinophil level in bronchoalveolar lavage. Both HiTr and OVA intervention upregulated circulating NGF level and peripherin level in adrenal medulla, but downregulated phenylethanolamine N-methyl transferase level in adrenal medulla and circulating EPI level. HiTr ϩ OVA and HiTr ϩ ExhEx (exhaustive exercise) interventions significantly enhanced most of the HiTr effects. The elevated NGF level was significantly associated with neuronal conversion of adrenal medulla chromaffin cells (AMCC). The levels of p-Erk1/2, JMJD3, and Mash1 were significantly increased, but the levels of p-p38 and p-JNK were significantly decreased in adrenal medulla in HiTr and OVA rats. Injection of NGF antiserum and moderate-intensity training reversed these changes observed in HiTr and/or OVA rats. Our study suggests that NGF may play a vital role in the pathogenesis of EIB by inducing neuron transdifferentiation of AMCC via MAPK pathways and subsequently decreasing circulating EPI. exercise; asthma; lung; inflammation; NGF; neuron conversion; adrenal medulla EXERCISE-INDUCED BRONCHOCONSTRICTION (EIB) is the increase in airway obstruction with symptoms of coughing, wheezing, or dyspnea as a result of exercise (23). EIB occurs in ϳ11% of the general population without asthma (13). Inhalation of cold air and sudden changes in humidity or temperature have been associated with EIB (20). High prevalence of EIB is usually observed among endurance athletes (7), implicating that intensity of exercise may be associated with EIB.Although thermal and osmotic consequences of water loss play prominent roles in the emergence of EIB (2), more studies are needed to elucidate the underlying mechanism. Circulating epinephrine (EPI), produced by adrenal medulla chromaffin cells (AMCC), is believed to bind the adrenergic receptors of airway smooth muscles to achieve adrenergic bronchodilation, and a loss of this function could directly influence the sev...

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“…Moreover, maternal asthma during pregnancy has been shown to result in dysfunction of bronchial relaxation in offspring rats via inhibition of epinephrine synthesis. 47 Furthermore, maternal hypoxia has been shown to affect fetal growth, placental function, and length of gestation, [48][49][50] and these birth outcomes have been linked with adverse health outcomes in numerous studies. 51,52 Therefore, maternal hypoxia may, via restricted fetal oxygenation, result in multiple organ pathology that manifests in a wide range of offspring diseases.…”

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confidence: 99%

Asthma During Pregnancy and Clinical Outcomes in Offspring: A National Cohort Study

Tegethoff¹,

Olsen

Schaffner

et al. 2013

Pediatrics

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WHAT'S KNOWN ON THIS SUBJECT: Asthma is a common medical complication during pregnancy that is associated with an increased risk of adverse obstetric outcomes. WHAT THIS STUDY ADDS:This study adds knowledge on potential long-term consequences of maternal asthma during pregnancy for offspring health, demonstrating that maternal asthma during pregnancy is linked to a wide spectrum of offspring diseases during childhood. abstract BACKGROUND AND OBJECTIVE: Maternal asthma is a common pregnancy complication, with adverse short-term effects for the offspring. The objective was to determine whether asthma during pregnancy is a risk factor of offspring diseases. METHODS:We studied pregnant women from the Danish National Birth Cohort (births: 1996Cohort (births: -2002; prospective data) giving birth to live singletons (n = 66 712 mother-child pairs), with 4145 (6.2%) women suffering from asthma during pregnancy. We estimated the associations between asthma during pregnancy and offspring diseases (International Classification of Diseases, 10th Revision diagnoses from national registries), controlling for potential confounders and validating findings by secondary analyses. RESULTS:Offspring median age at end of follow-up was 6.2 (3.6-8.9) years. Asthma was associated with an increased offspring risk of infectious and parasitic diseases (hazard ratio [HR] 1.34; 95% confidence interval [CI] 1.23-1.46), diseases of the nervous system (HR 1.43; CI 1.18-1.73), ear (HR 1.33; CI 1.19-1.48), respiratory system (HR 1.43; CI 1.34-1.52), and skin (HR 1.39; CI 1.20-1.60), and potentially (not confirmed in secondary analyses) of endocrine and metabolic disorders (HR 1.26; CI 1.02-1.55), diseases of the digestive system (HR 1.17; CI 1.04-1.32), and malformations (odds ratio 1.13; CI 1.01-1.26), but not of neoplasms, mental disorders, or diseases of the blood and immune system, circulatory system, musculoskeletal system, and genitourinary system. CONCLUSIONS:To the best of our knowledge, this is the first comprehensive study of the associations between asthma during pregnancy and a wide spectrum of offspring diseases. In line with previous data on selected outcomes, asthma during pregnancy may be a risk factor for numerous offspring diseases, suggesting that careful monitoring of women with asthma during pregnancy and their offspring is important. Dr Tegethoff conceptualized and designed the study, carried out the statistical analyses, interpreted data, drafted the initial manuscript, critically reviewed the manuscript, and obtained funding; Dr Olsen acquired data, interpreted data, critically reviewed the manuscript, and obtained funding; Mr Schaffner carried out the statistical analyses, interpreted data, and critically reviewed the manuscript; Dr Meinlschmidt conceptualized and designed the study, carried out the statistical analyses, interpreted data, critically reviewed the manuscript, and obtained funding; and all authors approved the final manuscript as submitted. Asthma is a frequently occurring medical condition in pregnancy, ...

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Asthma Pregnancy Alters Postnatal Development of Chromaffin Cells in the Rat Adrenal Medulla

Cited by 7 publications

References 33 publications

The Effect of Unilateral Adrenalectomy on Transformation of Adrenal Medullary Chromaffin Cells In Vivo: A Potential Mechanism of Asthma Pathogenesis

The Effect of Unilateral Adrenalectomy on Transformation of Adrenal Medullary Chromaffin Cells In Vivo: A Potential Mechanism of Asthma Pathogenesis

High-intensity training induces EIB in rats through neuron transdifferentiation of adrenal medulla chromaffin cells

Asthma During Pregnancy and Clinical Outcomes in Offspring: A National Cohort Study

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