[1]向涵,王绍,周玥,等.邻苯二甲酸二乙酯诱导的大鼠尿道下裂与Mafb的表达相关：基于转录组测序结果[J].南方医科大学学报,2019,(04):456.[doi:10.12122/j.issn.1673-4254.2019.04.12]
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邻苯二甲酸二乙酯诱导的大鼠尿道下裂与Mafb的表达相关：基于转录组测序结果()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2019年04期
页码:
456
栏目:
出版日期:
2019-04-26

文章信息/Info

Title:
Di (2-ethylhexyl) phthalate-induced hypospadias in SD rats is related with Mafb expression: a transcriptome profiling-based study
作者:
向涵; 王绍; 周玥; 刘星; 沈炼桔; 龙春兰; 张德迎; 何大维; 林涛; 魏光辉
关键词:
尿道下裂; 邻苯二甲酸二乙酯; 转录组测序; Mafb
Keywords:
hypospadias;  Di (2-ethylhexyl) phthalate;  RNA-seq;  Mafb
DOI:
10.12122/j.issn.1673-4254.2019.04.12
摘要:
目的通过转录组测序筛选大鼠尿道发育过程中相关差异基因，并进行验证；探究邻苯二甲酸二乙酯（DEHP）诱导SD大鼠 尿道下裂的发生机制。方法40只成年SD孕鼠随机分成4组（n=10），前两组予以空白对照处理，分别于妊娠期16 d（GD16组） 和GD19 d（GD19组）剖宫产取出雄性胎鼠，将收集好的胎鼠阴茎组织进行转录组测序，lllumina HiSeq 2000筛选出差异表达基 因（DEGs），然后对DEGs进行差异基因功能（GO）和pathway显著富集性分析；选取其中的DEG（Mafb）进行免疫荧光验证。后 两组分别予以玉米油（对照组）和DEHP [750 mg/(kg·d)]（DEHP暴露组）于GD12 d至GD19 d每日灌胃处理，GD19 d剖宫产取 出雄性胎鼠，并判断有无尿道下裂的发生。扫描电镜和HE染色观察阴茎组织形态学改变，免疫荧光和Western blot检验阴茎组 织中Mafb、β-catenin的表达水平。结果GD19组胎鼠阴茎组织与GD16组胎鼠阴茎组织转录组测序结果示1360个DEGs（其中 上调797个，下调563个），差异基因主要富集于细胞粘着斑信号通路、轴突导向信号通路、细胞外基质受体作用信号通路等，选 取DEG（Mafb）进行免疫荧光验证，发现Mafb的表达随发育显著增加，与测序结果相符。而DEHP暴露组胎鼠阴茎组织与对照 组胎鼠阴茎组织相比，Mafb、β-catenin表达水平显著下调（P<0.01）。结论随着大鼠阴茎组织的正常发育，Mafb的表达逐渐增 加；而DEHP暴露组较对照组Mafb、β-catenin表达显著下调，提示β-catenin信号通路影响Mafb表达可能与DEHP诱导大鼠尿道 下裂发生相关。
Abstract:
Objective To investigate the transcriptome profile of genital tubercles (GTs) in male SD rats and explore the mechanism of hypospadias induced by Di (2-ethylhexyl) phthalate (DEHP). Methods Forty time-pregnant SD rats were randomly divided into 4 equal groups, namely GD16 group and GD19 group (in which the male GTs were collected on gestation day [GD] 16 and GD19 for RNA-seq, respectively), control group and DEHP exposure group (with administration of oil and 750 mg/kg DEHP by gavage from GD12 to GD19, respectively). In the control and DEHP exposure groups, the GTs were collected from the male fetuses on GD19.5, and scanning electron microscopy and HE staining were used to observe the morphological changes. The differentially expressed genes (DEGs) in the GTs were screened using lllumina HiSeq 2000 followed by GO and KEGG enrichment analyses to characterize the transcriptome profile. Immunofluorescence assay was performed to verify the DEGs (Mafb) identified by RNA-seq results. Immunofluorescence assay and Western blotting were used to examine the expression levels of Mafb in the penile tissue. Results A total of 1360 DEGs were detected in the GTs between GD16 group and GD19 group by RNA-seq. Among these genes, 797 were up-regulated and 563 were down-regulated. These DEGs were mainly enriched in the cell adhesion plaque signaling pathway, axon guidance signaling pathway, and extracellular matrix receptor signaling pathway. Compared with that in GD16 group, Mafb was significantly up-regulated in GD19 group, which was consistent with the sequencing results. Mafb and β-catenin were significantly down-regulated in DEHP-exposed group compared with the control group (P<0.01). Conclusion Mafb expression increases progressively with the development of GTs in male SD rats. DEHP exposure causes significant down-regulation of Mafb and β-catenin, suggesting that β-catenin signaling pathway that affects Mafb is related to DEHP-induced hypospadias in SD rats.

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更新日期/Last Update: 1900-01-01