Department of Health Sciences, Division of Obstetrics and Gynecology, Careggi Hospital, University of Florence, Florence, Italy.
Department of Statistics, Computer Science, Applications, University of Florence, Florence, Italy.
J Reprod Immunol. 2022 Sep;153:103692. doi: 10.1016/j.jri.2022.103692. Epub 2022 Aug 6.
Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are key enzymes for tryptophan degradation, regulating immune tolerance during pregnancy. The intrauterine renin-angiotensin system is also involved in the progression of a healthy pregnancy. Angiotensin(1-7) maintains the integrity of fetal membranes via counteracting the pro-inflammatory actions of Angiotensin II. No data are available on placental Angiotensin(1-7) co-expression with TDO. We aimed to characterize TDO mRNA expression and its localization in different areas of the placenta of physiological pregnancies delivered at term; its co-expression with Angiotensin(1-7) and its correlation with the plasma kynurenine/tryptophan (Kyn/Trp) ratio was investigated. This prospective observational study included a nonconsecutive series of 20 singleton uncomplicated pregnancies delivered vaginally. TDO mRNA was expressed in both maternal and fetal sides of the placentas and TDO protein also in the villi and it was co-expressed with IDO1 in almost half of the placental cells at these sites. The percentage of TDO and IDO1 cells appeared to be influenced by maternal pre-gestational smoking and newborn weight. A strong correlation was found between the percentage of TDO and IDO1 cells in the villi. TDO cells also expressed Angiotensin(1-7), with a higher percentage on the fetal side and in the villi compared to the maternal one. Kyn/Trp plasma ratio was not correlated with IDO and TDO expression nor with the patient's characteristics. Collectively, our data indicate that TDO is detectable in placental tissue and is co-expressed with IDO and with Angiotensin(1-7) on the fetal side and in the villi.
色氨酸 2,3-双加氧酶 1（IDO1）和色氨酸 2,3-双加氧酶（TDO）是色氨酸降解的关键酶，调节妊娠期间的免疫耐受。子宫内肾素-血管紧张素系统也参与了健康妊娠的进展。血管紧张素（1-7）通过抵消血管紧张素 II 的促炎作用来维持胎儿膜的完整性。目前尚无关于胎盘血管紧张素（1-7）与 TDO 共表达的资料。我们旨在描述 TDO mRNA 在足月生理性妊娠胎盘不同区域的表达及其定位；研究其与血管紧张素（1-7）的共表达及其与血浆犬尿氨酸/色氨酸（Kyn/Trp）比值的相关性。这项前瞻性观察性研究包括了 20 例非连续的经阴道分娩的单胎正常妊娠。TDO mRNA 在胎盘的母体和胎儿侧均有表达，TDO 蛋白也在绒毛中表达，在这些部位的近一半胎盘细胞中与 IDO1 共表达。TDO 和 IDO1 细胞的百分比似乎受到孕妇孕前吸烟和新生儿体重的影响。在绒毛中，TDO 和 IDO1 细胞的百分比之间存在很强的相关性。TDO 细胞也表达血管紧张素（1-7），在胎儿侧和绒毛中的表达百分比高于母体侧。Kyn/Trp 血浆比值与 IDO 和 TDO 表达以及患者特征均无相关性。总之，我们的数据表明 TDO 可在胎盘组织中检测到，并与 IDO 和胎儿侧及绒毛中的血管紧张素（1-7）共表达。
