Murthi Padma, Wallace Euan M, Walker David W
Department of Medicine, School of Clinical Sciences, Monash University, Monash Medical Centre, Clayton, Victoria, 3168, Australia; The Ritchie Centre, Hudson Institute of Medical Research, 27-31 Wright St., Clayton, Victoria, 3168, Australia.
The Ritchie Centre, Hudson Institute of Medical Research, 27-31 Wright St., Clayton, Victoria, 3168, Australia; Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, 3168, Australia.
Placenta. 2017 Apr;52:62-70. doi: 10.1016/j.placenta.2017.02.013. Epub 2017 Feb 16.
Tryptophan is a substrate for kynurenine pathway metabolism in the placenta. We investigated if kynurenine metabolites change over gestation, if they are different between pregnancies with normal and fetal growth restriction (FGR), and if the oxygen environment modulated kynurenine pathway activity in the human placenta.
Tryptophan, kynurenine, and downstream kynurenine metabolites were determined in maternal venous blood, umbilical cord blood, and placental samples obtained in 1st and 3rd trimester pregnancies including FGR, and in the media of placental explants incubated with 20% or 5-8% O for 24, 48 or 72 h.
All the major kynurenine metabolites were present in cord blood, and in general were higher than in maternal blood. IDO and TDO mRNA and protein expression, responsible for kynurenine production from tryptophan, were significantly lower in placentas from FGR pregnancies compared with control. Explants prepared from 1st and 3rd trimester placentas actively produced all the major kynurenine pathway metabolites which, together with expression of IDO, TDO, KYN-OHase and 3HAO mRNAs, were significantly lower after 24 h exposure to 5-8% O compared to 20% O CONCLUSIONS: Expression and activity of the kynurenine pathway is present in the placenta from early gestation, and is down-regulated by hypoxia and in FGR pregnancies.
色氨酸是胎盘中犬尿氨酸途径代谢的底物。我们研究了犬尿氨酸代谢产物在孕期是否会发生变化，在正常妊娠与胎儿生长受限（FGR）妊娠之间是否存在差异，以及氧环境是否会调节人胎盘的犬尿氨酸途径活性。
在孕早期和孕晚期获取的孕妇静脉血、脐带血及胎盘样本（包括FGR妊娠）中，以及在分别用20%或5 - 8%氧气孵育24、48或72小时的胎盘外植体培养基中，测定色氨酸、犬尿氨酸及下游犬尿氨酸代谢产物。
所有主要的犬尿氨酸代谢产物均存在于脐带血中，且总体上高于母血中的水平。与对照组相比，FGR妊娠胎盘组织中负责从色氨酸生成犬尿氨酸的吲哚胺2,3-双加氧酶（IDO）和色氨酸2,3-双加氧酶（TDO）的mRNA和蛋白表达显著降低。孕早期和孕晚期胎盘制备的外植体均能活跃地产生所有主要的犬尿氨酸途径代谢产物，与20%氧气环境相比，在5 - 8%氧气环境中暴露24小时后，这些代谢产物以及IDO、TDO、犬尿氨酸-3-单加氧酶（KYN-OHase）和3-羟基犬尿氨酸3,4-双加氧酶（3HAO）的mRNA表达均显著降低。
犬尿氨酸途径的表达和活性在妊娠早期的胎盘中即已存在，且在缺氧及FGR妊娠中会下调。
