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子宫内膜上皮中的脂肪酸结合蛋白4参与胚胎着床。

Fatty Acid-Binding Protein 4 in Endometrial Epithelium Is Involved in Embryonic Implantation.

作者信息

Wang Peng, Zhu Qiuyuan, Peng Huilian, Du Mengkai, Dong Minyue, Wang Hanzhi

出版信息

Cell Physiol Biochem. 2017;41(2):501-509. doi: 10.1159/000456886. Epub 2017 Jan 30.

Abstract

AIMS

To clarify the role of fatty acid-binding protein 4 (FABP4) of endometrial epithelial cell in the establishment and maintenance of pregnancy and the involvement in the pathogenesis of pregnancy loss.

METHODS

The expression of FABP4 and uterine receptive factor (LIF, Integrin-β3 and Claudin 4) was determined by Western blotting or quantitative PCR. FABP4 siRNA was used to silence FABP4 while FABP4 inhibitor was used to inhibit the function of FABP4 in endometrial epithelial cell. ICR mice were raised to evaluate the effect of FABP4 silence or inhibition on embryo implantation in vivo after FABP4 siRNA mixture or inhibitor was injected into uterus, and an embryonic adhesion system using trophoblast spheroids mimicking embryos was set up to assess the effect of FABP4 silence or inhibition on embryonic adhesion onto endometrial cell in vitro.

RESULTS

The expression of FABP4 mRNA was significantly decreased in the deciduas of women with pregnancy loss compared with that of women with normal pregnancy. FABP4 siRNA significantly reduced the number of embryos implanted and FABP4 expression in ICR mice. FABP4 inhibition also significantly decreased the number of embryos implanted. Either silence or inhibition of FABP4 in endometrial epithelial cell abolished the expression of uterine receptive factors induced by the combination of estrogen and progesterone-induced, and reduced the number of trophoblast spheroids adhered onto endometrial cell.

CONCLUSIONS

FABP4 regulates embryo implantation via altering uterine receptivity and decreased expression of FABP4 in endometrium may be linked with pregnancy loss, indicating FABP4 has biological role in the establishment and maintenance of pregnancy and subsequently is involved in pathogenesis of pregnancy loss.

摘要

目的

阐明子宫内膜上皮细胞脂肪酸结合蛋白4(FABP4)在妊娠建立和维持中的作用以及在妊娠丢失发病机制中的参与情况。

方法

采用蛋白质免疫印迹法或定量PCR检测FABP4及子宫接受因子(白血病抑制因子、整合素β3和闭合蛋白4)的表达。利用FABP4小干扰RNA沉默FABP4,同时使用FABP4抑制剂抑制子宫内膜上皮细胞中FABP4的功能。饲养ICR小鼠,在向子宫注射FABP4小干扰RNA混合物或抑制剂后,评估FABP4沉默或抑制对体内胚胎着床的影响,并建立使用模拟胚胎的滋养层球体的胚胎黏附系统,以评估FABP4沉默或抑制对体外胚胎黏附于子宫内膜细胞的影响。

结果

与正常妊娠女性相比,妊娠丢失女性蜕膜中FABP4 mRNA表达显著降低。FABP4小干扰RNA显著减少了ICR小鼠体内植入的胚胎数量及FABP4表达。FABP4抑制也显著降低了植入的胚胎数量。子宫内膜上皮细胞中FABP4的沉默或抑制均消除了雌激素和孕激素联合诱导的子宫接受因子的表达,并减少了黏附于子宫内膜细胞的滋养层球体数量。

结论

FABP4通过改变子宫接受性来调节胚胎着床,子宫内膜中FABP4表达降低可能与妊娠丢失有关,表明FABP4在妊娠建立和维持中具有生物学作用,并随后参与妊娠丢失的发病机制。

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