Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Placenta. 2021 Nov;115:129-138. doi: 10.1016/j.placenta.2021.09.008. Epub 2021 Sep 14.
The human placenta performs multiple functions necessary for successful pregnancy, but the metabolic pathways and molecular mechanisms responsible for regulating placental development and functions remain incompletely understood. Catabolism of the essential amino acid tryptophan has numerous critical roles in normal physiology, including inflammation. The kynurenine pathway, which accounts for ∼90% of tryptophan breakdown, is mediated by indoleamine 2,3 dioxygenase 1 (IDO1) in the placenta. In pregnant mice, alterations of IDO1 activity or expression result in fetal resorption and a preeclampsia-like phenotype. Decreased IDO1 expression at the maternal-fetal interface has also been linked to preeclampsia, in utero growth restriction and recurrent miscarriage in humans. These collective observations suggest essential role(s) for IDO1 in maintaining healthy pregnancy. Despite these important roles, the precise temporal, cell-specific and inflammatory cytokine-mediated patterns of IDO1 expression in the human placenta have not been thoroughly characterized across gestation.
Western blot and whole mount immunofluorescence (WMIF) were utilized to characterize and quantify basal and interferon (IFN)-inducible IDO1 expression in 1st trimester (7-13 weeks), 2nd trimester (14-22 weeks) and term (39-41 weeks) placental villi.
IDO1 expression is activated in the human placenta between the 13th and 14th weeks of pregnancy, increases through the 2nd trimester and remains elevated at term. Constitutive IDO1 expression is restricted to placental endothelial cells. Interestingly, different types of IFNs have distinct effects on IDO1 expression in the human placenta.
Our collective results are consistent with potential role(s) for IDO1 in the regulation of vascular functions in placental villi.
人类胎盘具有多种功能，这些功能对于成功妊娠是必要的，但负责调节胎盘发育和功能的代谢途径和分子机制仍不完全清楚。必需氨基酸色氨酸的分解代谢在正常生理中具有许多关键作用，包括炎症。色氨酸分解代谢的犬尿氨酸途径，由胎盘内的吲哚胺 2,3 双加氧酶 1（IDO1）介导。在妊娠小鼠中，IDO1 活性或表达的改变导致胎儿吸收和子痫前期样表型。母体-胎儿界面 IDO1 表达的减少也与子痫前期、宫内生长受限和人类复发性流产有关。这些观察结果表明 IDO1 在维持健康妊娠中起着重要作用。尽管有这些重要作用，但 IDO1 在人类胎盘中的表达在整个妊娠过程中的时间、细胞特异性和炎症细胞因子介导模式尚未得到彻底描述。
利用 Western blot 和全胎盘免疫荧光（WMIF）技术，对 1 期（7-13 周）、2 期（14-22 周）和 3 期（39-41 周）胎盘绒毛中的基础和干扰素（IFN）诱导型 IDO1 表达进行了特征描述和定量。
IDO1 表达在妊娠的第 13 至 14 周在人胎盘内被激活，在第 2 孕期增加，并在第 3 孕期保持升高。组成性 IDO1 表达局限于胎盘内皮细胞。有趣的是，不同类型的 IFN 对人胎盘 IDO1 表达有不同的影响。
我们的综合结果表明 IDO1 在胎盘绒毛血管功能调节中可能发挥作用。
