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

et al. (2011) Asthma Pregnancy Alters Postnatal Development of Chromaffin Cells in the Rat Adrenal Medulla. PLoS ONE 6(5): e20337. doi:10.1371/journal.pone.0020337 Asthma Pregnancy Alters Postnatal Development of Chromaffin Cells in the Rat Adrenal Medulla Xiu-Ming Wu. 0 Cheng-Ping Hu. 0 Xiao-Zhao Li 0 Ye-Qiang Zou 0 Jun-Tao Zou 0 Yuan-Yuan Li 0 Jun-Tao Feng 0 Rory Edward Morty, University of Giessen Lung Center, Germany 0 Department of Respiratory Medicine, Xiangya Hospital, Central South University , Changsha, Hunan , China Background: Adrenal neuroendocrine plays an important role in asthma. The activity of the sympathoadrenal system could be altered by early life events. The effects of maternal asthma during pregnancy on the adrenal medulla of offspring remain unknown. Methodology/Principal Findings: This study aims to explore the influence of maternal asthma during pregnancy on the development and function of adrenal medulla in offspring from postnatal day 3 (P3) to postnatal day 60 (P60). Asthmatic pregnant rats (AP), nerve growth factor (NGF)-treated pregnant rats (NP) and NGF antibody-treated pregnant rats (ANP) were sensitized and challenged with ovalbumin (OVA); NP and ANP were treated with NGF and NGF antibody respectively. Offspring rats from the maternal group were divided into four groups: offspring from control pregnant rats (OCP), offspring from AP (OAP), offspring from NP (ONP), and offspring from ANP (OANP). The expressions of phenylethanolamine Nmethyltransferase (PNMT) protein in adrenal medulla were analyzed. The concentrations of epinephrine (EPI), corticosterone and NGF in serum were measured. Adrenal medulla chromaffin cells (AMCC) were prone to differentiate into sympathetic nerve cells in OAP and ONP. Both EPI and PNMT were decreased in OAP from P3 to P14, and then reached normal level gradually from P30 to P60, which were lower from birth to adulthood in ONP. Corticosterone concentration increased significantly in OAP and ONP. Conclusion/Significance: Asthma pregnancy may promote AMCC to differentiate into sympathetic neurons in offspring rats and inhibit the synthesis of EPI, resulting in dysfunction of bronchial relaxation. - Funding: This work was supported by National Natural Science Foundation of China (No. 30800502, No. 30801505 and No. 81070026). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. . These authors contributed equally to this work. Asthma is a disease with its origins in early life. Maternal asthma is a risk factor for asthma in children [1]. Study demonstrated that some components in uterus or early postnatal environment might cause increase of asthma susceptibility in offspring [2]. Epigenetic studies suggested that environmental factors exposed to pregnant mothers were closely related to the childhood asthmatic phenotypes, especially after the birth [3,4]. However, the pathogenesis is complex and not entirely understood. Adrenal neuroendocrine played an important role in the regulation of bronchial diastole by secreting epinephrine (EPI) [5]. Recent reports demonstrated that the activity of the sympathoadrenal system could be altered by early life event; Sympathetic adrenal cells, derived from embryonic neural crest stem cells, could migrate and locate into adrenal gland during the development [6]. After the lost of neurons features, those cells differentiate into adrenal medulla chromaffin cells (AMCC) with endocrine function [7]. However, experimental study indicated that AMCC have redundant functions in the setting of abnormal physiological functions, including loss of endocrine phenotype and acquisition of neuronal properties [8,9]. Studies indicated that continuous infusion of nerve growth factor (NGF) into 17 days pregnant rats enhanced the transformation of AMCC into sympathetic neurons, which then infiltrated into adrenal cortex and medulla and altered their structures [10].The alteration in the early sympathetic-adrenal system activity, development, and maturation partly attribute to environmental stimulation during uterus and after birth[11,12]. The development and maintenance of AMCC are critically dependent NGF. Circulating NGF levels are increased in humans with allergic diseases and asthma [13]. Investigation recently found that increased NGF in asthma could induce functional redundancy of rat AMCC, which resulting in transforming them into sympathetic neurons, and significantly reduced the synthesis and release of EPI, unbalancing bronchial contraction and relaxation[14,15].Exposure to high level of NGF in the intrauterine environment may play an important role in the process of neural stem cell growth, migration and development and the differentiation of AMCC into sympathetic neurons, interfering with the synthesis, storage, release of EPI, even participating in adult bronchia (...truncated)