COUP-TFI deletion affects angiogenesis and apoptosis related gene expression in mouse placenta: results of an explorative study

IF 0.4 4区 医学 Q4 OBSTETRICS & GYNECOLOGY
L. Viola, S. Marzinotto, M. Bertacchi, A. Londero, M. Orsaria, S. Bertozzi, L. Driul, C. di Loreto, M. Studer, L. Mariuzzi, A. Fruscalzo
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引用次数: 2

Abstract

Background: Chicken Ovalbumin Upstream Promoter-Transcription Factor I (COUP-TFI) is a member of the steroid/thyroid nuclear receptor superfamily. The aim of this study was to investigate whether absence of this gene affects placental development and fetal growth in a COUP-TFI knockout mouse model. Methods: Placentas of COUP-TFI-knockout (COUP-TFI KO) and wild-type (WT) were collected at 18.5 days post-coitum. The expression level of the following genes known to be involved in different key molecular pathways was evaluated: BCL2Associated X (Bax) and B-cell lymphoma 2 (Bcl-2) (apoptosis), p21, p53 andα subunit of inhibin (INHA) (proliferation and apoptosis), vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF), hypoxia-inducible factor 1-alpha (HIF1α), Fms related receptor tyrosine kinase 1 (Flt-1), and endoglin (ENG) (angiogenesis). Mouse litter weight at birth was also assessed. Results: RT-qPCR analysis showed increased mRNA expression of VEGF-A and Bax in placental tissue of COUP-TFI KO mice compared to WT mice. We also found a loss in the positive correlation between Bcl-2 and INHA, p21 and ENG, as well as HIF1α and Flt-1 mRNA expression in COUP-TFI mutants. Finally, KO mice were lighter than WT littermates (respectively, the mean weight of COUP-TFI KOmice was 1.3 grams,± 0.13, compared to 1.6 g,± 0.14 ofWTmice, p< 0.05). Conclusions: Our results show that COUP-TFI deletion is associated with a lower birth weight in mice and increased placental transcript expression of pro-apoptotic Bax and pro-angiogenetic VEGF-A genes.
COUP-TFI缺失影响小鼠胎盘血管生成和凋亡相关基因表达的探索性研究结果
背景:鸡卵清蛋白上游启动子转录因子I(COUP-TFI)是类固醇/甲状腺核受体超家族的成员。本研究的目的是研究该基因的缺失是否会影响COUP-TFI敲除小鼠模型中的胎盘发育和胎儿生长。方法:在交配后18.5天采集COUP-TFI敲除(COUP-TFI-KO)和野生型(WT)胎盘。评估了已知参与不同关键分子途径的以下基因的表达水平:BCL2相关X(Bax)和B细胞淋巴瘤2(Bcl-2)(凋亡)、p21、p53和抑制素α亚基(INHA)(增殖和凋亡)、血管内皮生长因子A(VEGF-A)、胎盘生长因子(PlGF)、缺氧诱导因子1α,Fms相关受体酪氨酸激酶1(Flt-1)和endoglin(ENG)(血管生成)。还对出生时的小鼠产仔重量进行了评估。结果:RT-qPCR分析显示,与WT小鼠相比,COUP-TFI KO小鼠胎盘组织中VEGF-A和Bax的mRNA表达增加。我们还发现,在COUP-TFI突变体中,Bcl-2与INHA、p21与ENG以及HIF1α和Flt-1mRNA表达之间的正相关性缺失。最后,KO小鼠比同窝出生的WT小鼠轻(COUP-TFI KO小鼠的平均体重分别为1.3克,±0.13,而WT小鼠的平均重量为1.6克,±0.14,p<0.05)。
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来源期刊
CiteScore
0.50
自引率
0.00%
发文量
241
审稿时长
1 months
期刊介绍: CEOG is an international, peer-reviewed, open access journal. CEOG covers all aspects of Obstetrics and Gynecology, including obstetrics, prenatal diagnosis, maternal-fetal medicine, perinatology, general gynecology, gynecologic oncology, uro-gynecology, reproductive medicine, infertility, reproductive endocrinology, sexual medicine. All submissions of cutting-edge advances of medical research in the area of women''s health worldwide are encouraged.
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