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雌激素通过细胞因子信号转导抑制因子 3 诱导早孕绒毛和蜕膜中吲哚胺 2,3-双加氧酶的表达。

Estrogen induces indoleamine 2,3-dioxygenase expression via suppressors of cytokine signaling 3 in the chorionic villi and decidua of women in early pregnancy.

机构信息

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

Department of Obstetrics and Gynecology, Affiliated Hospital of Guizhou Medical University, Guiyang, China.

出版信息

Am J Reprod Immunol. 2020 Jan;83(1):e13197. doi: 10.1111/aji.13197. Epub 2019 Nov 2.

DOI:10.1111/aji.13197
PMID:31599074
Abstract

PROBLEM

Indoleamine 2,3-dioxygenase (IDO) is a key protein that participates in the protection of embryos against the mother's immune system during pregnancy. How the expression of this protein is regulated at the maternal-fetal interface remains largely unknown.

METHOD OF STUDY

The chorionic villi and decidua of women in early pregnancy were collected. Tissue explants of the chorionic villi and decidua were cultured in media containing varying concentrations of 17β-estradiol and estriol with or without fulvestrant. Western blot analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the expression of IDO and the suppressors of cytokine signaling 3 (SOCS3) in the cultured tissues from chorionic villi and decidua.

RESULTS

Both IDO and SOCS3 were expressed in chorionic villi and decidua. The expression of IDO was increased in tissue explants from chorionic villi and decidua cultured in medium containing different concentrations of 17β-estradiol or estriol, and this increase was reversed when fulvestrant was added to the medium. The expression of IDO was upregulated, and SOCS3 expression was downregulated the most in tissue explants from chorionic villi and decidua that were cultured in medium containing 17β-estradiol at a concentration of 10 ng/mL or estriol at a concentration of 1 µg/mL. This increase in IDO and decrease in SOCS3 were reversed when fulvestrant was added to the medium at a concentration of 10 µg/mL.

CONCLUSION

At a concentration similar to that present during pregnancy, estrogen may upregulate the expression of IDO via downregulating SOCS3, which implies that estrogen may contribute to the prevention of allogeneic fetal rejection, and further studies may strengthen the possibility of using estrogen as an immune modulator.

摘要

问题

色氨酸 2,3-双加氧酶 (IDO) 是一种关键蛋白,它参与了胚胎在怀孕期间免受母体免疫系统攻击的保护。这种蛋白的表达如何在母体-胎儿界面受到调节在很大程度上仍是未知的。

方法

收集早孕妇女的绒毛膜和蜕膜组织。绒毛膜和蜕膜组织的组织外植体在含有不同浓度 17β-雌二醇和雌三醇的培养基中与或不与氟维司群一起培养。使用 Western blot 分析和定量逆转录聚合酶链反应 (qRT-PCR) 检测绒毛膜和蜕膜组织培养物中 IDO 和细胞因子信号转导抑制物 3 (SOCS3) 的表达。

结果

IDO 和 SOCS3 均在绒毛膜和蜕膜中表达。在含有不同浓度 17β-雌二醇或雌三醇的培养基中培养的绒毛膜和蜕膜组织外植体中,IDO 的表达增加,而当培养基中加入氟维司群时,这种增加被逆转。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组织外植体中,IDO 的表达上调,SOCS3 的表达下调最为明显。当培养基中加入氟维司群浓度为 10μg/mL 时,IDO 的增加和 SOCS3 的减少被逆转。

结论

在类似于妊娠期间存在的浓度下,雌激素可能通过下调 SOCS3 来上调 IDO 的表达,这表明雌激素可能有助于防止同种异体胎儿排斥,进一步的研究可能会增加使用雌激素作为免疫调节剂的可能性。

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