| Background:Adrenal neuroendocrine played an important role in asthma. Epigenetic studies suggest that abnormality in maternal intrauterine environment during fetal period can imprint occurrence of adult diseases.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 play a role in blocked adrenaline synthesis, imbalance between bronchial systolic and diastolic function, aggravating asthma severity.Subject:This study aims to explore the influence of maternal asthma during pregnancy on the development of adrenal medulla development of offspring and the differentiation of adrenal medulla cells (AMCC) to sympathetic neurons in adult offspring asthma.Methods:32SD rats were randomly divided into four groups:Asthmatic pregnancy 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. Rats were select from every pregnant group offspring at random and were divided into four groups(n=40per group):offspring from control pregnant rats (OCP), offspring from AP (OAP), offspring from NP (ONP), offspring from ANP (OANP).Adrenal glands were obtained for electron microscopic examination. The expression of NGF, phenylethanolamine N-methyltransferase (PNMT), peripherin and Rho GDIa were were analyzed by immunohistochemistry combine with the micro-image analysis. The concentration of epinephrine (EPI), NGF and corticosterone in serum were measured by ELISA.Result:1. Serum epinephrine levels were not significantly increased in AP group, electron microscopy show swelled mitochondria, decreased chromaffin granules, appearance of processes like change on adrenal medulla chromaffin cells. Serum epinephrine levels decreased in AP group. NP rats showed an aggravation of above mentioned pathological changes, while NP group NGF showed improved such changes.2. The adrenal medulla cells of OAP and ONP rats showed edema of cytoplasm and mitochondrial, vacuolar degeneration, deceased EPI secretory granule. chromaffin cells appeared fiber outgrowth and changed into spindle shape with long fusiform nucleus from postnatal day3(P3) to postnatal day14(P14). From postnatal day30(P30) to postnatal day60(P60), vacuolar degeneration showed decreased and the PEI secretory granule become increasing. Serum levels of EPI decreased in OAP rats from P3to P147compared to OCP rats and regained normal level from P30to P60; however, in ONP rats, from P3to P60, serum levels of EPI were lower than those in OCP rats. Serum levels of NGF increased from P3to P7in OAP and ONP rats and regained normal level from P14to P60. Serum levels of corticosterone in OAP and ONP rats increased significantly compared to OCP rats from P3to P60.The expression of PNMT proteins in the OAP and ONP rats adrenal medulla decreased significantly compared to OCP rats from P3to P14and gradually increased in OAP rats from P30to P60, there was a trend towards a lower expression in ONP rats. The expression of NGF increased in OAP and ONP rats adrenal medulla compared to OCP rats from P3to P14and return to normal level from P30to P60.3. After OVA sensitization and challenge, adult OAP and ONP rats showed significant Airway hyperresponsiveness and airway inflammation. The increase of vacuolar degeneration and lipid in adrenal medulla cells were observed in in OAP and ONP rats, Electron microscopy studies showed that AMCC presented signs of lesions:swelling mitochondrion, increased lipid, decreased EPI chromaffin granules in OAP and ONP rats. AMCC showed significant neuronal phenotype, EPI secretory granules even disappeared in ONP rats. ONP rats significantly reduced the expression of PNMT compared to OCP rats and NGF was significantly higher in ONP rats than OCP rats. Serum levels of EPI decreased in ONP rats. Serum levels of corticosterone in ONP rats increased significantly compared to OCP rats.4. The expression of peripherin increased in OAP and ONP rats adrenal medulla cells compared to OCP rats from P3to P14and return to normal level from P30to P60in OAP rats. However, the expression of peripherin in ONP rats increased from P30to P60compared to OCP. The expressions of peripherin in OANP rats increased from P3to P14compared to OAP. After OVA sensitization and challenge, the expression of peripherin increased in adult OAP and ONP rats compared to OCP rats and ONP rats showed more expression than OAP rats.The expression of Rho GDIa in the OAP and ONP rats adrenal medulla reduced significantly compared to OCP rats from P3to P14and gradually increased in OAP rats from P30to P60, there was a trend towards a lower expression in ONP rats from P30to P60. The expression of Rho GDIa in the OANP rats increased significantly compared to OAP rats from P3to P14and showed no difference from P30to P60. After OVA sensitization and challenge, OAP and ONP rats significantly reduced the expression of Rho GDIa in adrenal medulla and there was a trend towards a lower expression in ONP rats.Conclusion: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 the differentiation of AMCC into sympathetic neurons, interfering with the synthesis, storage, release of EPI, even participating in adult bronchial asthma in offspring rats after OVA sensitization and challenge. Peripherin and Rho GDIa may play an important role in the differentiation of AMCC of the offspring from asthmatic pregnant rats. |
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