As a crucial transcription factor for spermatogenesis,GATA-binding protein 4(GATA4)plays important roles in the functioning of Sertoli and Leydig cells.Conditional knockout of GATA4 in mice results in age-dependent te...As a crucial transcription factor for spermatogenesis,GATA-binding protein 4(GATA4)plays important roles in the functioning of Sertoli and Leydig cells.Conditional knockout of GATA4 in mice results in age-dependent testicular atrophy and loss of fertility.However,whether GATA4 is associated with human azoospermia has not been reported.Herein,we analyzed the GATA4 gene by direct sequencing of samples obtained from 184 Chinese men with idiopathic nonobstructive azoospermia(NOA).We identified a missense mutation(c.191G>A,p.G64E),nine single-nucleotide polymorphisms(SNPs),and one rare variant(c.^(*)84C>T)in the 3′untranslated region(UTR).Functional studies demonstrated that the p.G64E mutation did not affect transactivation ability of GATA4 for spermatogenesis-related genes(claudin-11 and steroidogenic acute regulatory protein,Star),and the 3′UTR rare variant c.^(*)84C>T did not generate microRNA-binding sites to repress GATA4 expression.To our knowledge,this is the first report to investigate the association between GATA4 and azoospermia;our results indicate that mutations in GATA4 may not be pathogenic for NOA in Chinese men.展开更多
目的研究氟西汀(Fluoxetine,Flu)抑制野百合碱(Monocrotaline,MCT)诱导的大鼠右心室肥厚与(GATA binding protein 4)结合蛋白4(GATA-4)表达的关系。方法建立MCT诱导的慢性肺动脉高压大鼠模型。灌胃给予大鼠不同剂量的Flu,检测右心室肥...目的研究氟西汀(Fluoxetine,Flu)抑制野百合碱(Monocrotaline,MCT)诱导的大鼠右心室肥厚与(GATA binding protein 4)结合蛋白4(GATA-4)表达的关系。方法建立MCT诱导的慢性肺动脉高压大鼠模型。灌胃给予大鼠不同剂量的Flu,检测右心室肥厚指标和心室GATA-4蛋白表达水平。结果MCT诱导的大鼠右心指数及右心室GATA-4蛋白表达均比正常对照组显著增加,Flu剂量依赖地抑制了右心指数及右心室GATA-4表达增加,而各组间左心室和室间隔的GATA-4表达没有明显变化。结论选择性5-羟色胺再摄取抑制剂Flu抑制MCT诱导的大鼠右心室肥厚可能与抑制GATA-4表达有关。展开更多
基金This research was supported by the National Natural Science Foundation of China(No.81601337)the Fundamental Research Funds of Shandong University(No.2016HW006)+1 种基金the Key research and development program of Shandong Province(No.2019GSF108237)The authors thank all of the participants involved in this study.
文摘As a crucial transcription factor for spermatogenesis,GATA-binding protein 4(GATA4)plays important roles in the functioning of Sertoli and Leydig cells.Conditional knockout of GATA4 in mice results in age-dependent testicular atrophy and loss of fertility.However,whether GATA4 is associated with human azoospermia has not been reported.Herein,we analyzed the GATA4 gene by direct sequencing of samples obtained from 184 Chinese men with idiopathic nonobstructive azoospermia(NOA).We identified a missense mutation(c.191G>A,p.G64E),nine single-nucleotide polymorphisms(SNPs),and one rare variant(c.^(*)84C>T)in the 3′untranslated region(UTR).Functional studies demonstrated that the p.G64E mutation did not affect transactivation ability of GATA4 for spermatogenesis-related genes(claudin-11 and steroidogenic acute regulatory protein,Star),and the 3′UTR rare variant c.^(*)84C>T did not generate microRNA-binding sites to repress GATA4 expression.To our knowledge,this is the first report to investigate the association between GATA4 and azoospermia;our results indicate that mutations in GATA4 may not be pathogenic for NOA in Chinese men.
文摘目的研究氟西汀(Fluoxetine,Flu)抑制野百合碱(Monocrotaline,MCT)诱导的大鼠右心室肥厚与(GATA binding protein 4)结合蛋白4(GATA-4)表达的关系。方法建立MCT诱导的慢性肺动脉高压大鼠模型。灌胃给予大鼠不同剂量的Flu,检测右心室肥厚指标和心室GATA-4蛋白表达水平。结果MCT诱导的大鼠右心指数及右心室GATA-4蛋白表达均比正常对照组显著增加,Flu剂量依赖地抑制了右心指数及右心室GATA-4表达增加,而各组间左心室和室间隔的GATA-4表达没有明显变化。结论选择性5-羟色胺再摄取抑制剂Flu抑制MCT诱导的大鼠右心室肥厚可能与抑制GATA-4表达有关。
