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雌激素通过 TGF-β在妊娠早期的绒毛膜和蜕膜中诱导 IDO 表达。

Estrogen induces IDO expression via TGF‑β in chorionic villi and decidua during early stages of pregnancy.

机构信息

Department of Obstetrics and Gynecology, Reproductive Medicine Center, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China.

Department of Obstetrics and Gynecology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China.

出版信息

Int J Mol Med. 2020 Sep;46(3):1186-1196. doi: 10.3892/ijmm.2020.4658. Epub 2020 Jun 24.

Abstract

Indoleamine 2,3‑dioxygenase (IDO) is one of the most important proteins protecting the embryos from the mother's immune system during pregnancy; however, little is known about the regulation of expression of this protein at the maternal‑fetal interface. In the current study, chorionic villi and decidua were collected from women at early stages of pregnancy. Samples of chorionic villi and decidua were cultured in medium containing different concentrations of 17β‑estradiol and estriol respectively, with or without fulvestrant. Western blot analysis and/or immunofluorescent staining were used to detect the expression of transforming growth factor β (TGF‑β) and IDO in chorionic villi and decidua tissues. Both TGF‑β and IDO were expressed in chorionic villi and decidua. The expression levels of these two proteins increased the most in samples of chorionic villi and decidua cultured in medium containing 17β‑estradiol at the concentration of 10 ng/ml, or estriol at the concentration of 1 µg/ml. This increase could be reversed when fulvestrant was added in the medium at the concentration of 10 µg/ml. IDO expression increased in a dose‑dependent manner in tissue samples cultured in medium containing TGF‑β. The results of the current study revealed that administration of estrogen at doses similar to those observed in healthy pregnant women may upregulate the expression of IDO by TGF‑β, suggesting that estrogen may prevent allogeneic fetal rejection and may be used as an immunomodulator.

摘要

色氨酸 2,3-双加氧酶 (IDO) 是在妊娠期间保护胚胎免受母体免疫系统攻击的最重要的蛋白质之一;然而,对于这种蛋白质在母体-胎儿界面的表达调控知之甚少。在本研究中,从妊娠早期的妇女中收集绒毛膜和蜕膜组织。将绒毛膜和蜕膜组织样本分别在含有不同浓度 17β-雌二醇和雌三醇的培养基中培养,有或没有氟维司群。使用 Western blot 分析和/或免疫荧光染色来检测绒毛膜和蜕膜组织中转化生长因子β(TGF-β)和 IDO 的表达。TGF-β和 IDO 均在绒毛膜和蜕膜中表达。在含有 17β-雌二醇浓度为 10ng/ml 或雌三醇浓度为 1μg/ml 的培养基中培养的绒毛膜和蜕膜样本中,这两种蛋白的表达水平增加最多。当在培养基中加入浓度为 10μg/ml 的氟维司群时,这种增加可以被逆转。在含有 TGF-β的培养基中培养的组织样本中,IDO 的表达呈剂量依赖性增加。本研究的结果表明,给予与健康孕妇中观察到的剂量相似的雌激素可能通过 TGF-β上调 IDO 的表达,表明雌激素可能预防同种异体胎儿排斥反应,并可用作免疫调节剂。

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