METHODS: 68 placentas obtained at birth were analyzed using qPCR to determine the expression of kynurenine pathway enzymes. Cytokines and metabolites were quantified in plasma using high-sensitivity electroluminescence and ultra-performance liquid chromatography, respectively. Maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) throughout pregnancy and the post-partum. Associations between these factors were assessed using robust linear regression with ranked enzymes.
RESULTS: Low placental quinolinate phosphoribosyl transferase (QPRT), the enzyme responsible for degrading QUIN, was associated with higher IL-6 and higher QUIN/kynurenic acid ratios at the 3rd trimester. Moreover, women with severe depressive symptoms in the 3rd trimester had significantly lower placental expression of both QPRT and 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase (ACMSD); impaired activity of these two enzymes leads to QUIN accumulation.
CONCLUSIONS: Overall, our data support that a compromised placental environment, featuring low expression of critical kynurenine pathway enzymes is associated with increased levels of plasma cytokines and the dysregulated kynurenine metabolite pattern observed in depressed women during pregnancy.
方法:使用qPCR分析出生时获得的68个胎盘,以确定犬尿氨酸途径酶的表达。使用高灵敏度电致发光和超高效液相色谱法定量血浆中的细胞因子和代谢物,分别。在整个怀孕和产后期间,使用爱丁堡产后抑郁量表(EPDS)评估产妇的抑郁症状。使用具有排序酶的稳健线性回归评估这些因素之间的关联。
结果:胎盘喹啉酸磷酸核糖转移酶(QPRT)低,负责降解QUIN的酶,在妊娠晚期与更高的IL-6和更高的QUIN/犬尿烯酸比率相关。此外,妊娠晚期有严重抑郁症状的女性,QPRT和2-氨基-3-羧基羧酸-6-半醛脱羧酶(ACMSD)的胎盘表达均显著降低;这两种酶活性受损导致QUIN积累.
结论:总体而言,我们的数据支持胎盘环境受损,关键犬尿氨酸途径酶的低表达与妊娠期间抑郁妇女中观察到的血浆细胞因子水平升高和犬尿氨酸代谢异常模式相关。