AUTHOR=Ye Xiaofeng , Ma Chong , Guo Wenqi , Guo Yan , Li Dong-dong , Zhou Sihang , Hu Qingyu , Hong Yanjun , Xie Zhiyong , Wang Liping 

TITLE=Metabolomic analysis reveals potential role of immunometabolism dysregulation in recurrent pregnancy loss

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1476774

DOI=10.3389/fendo.2024.1476774

ISSN=1664-2392

ABSTRACT=Recurrent pregnancy loss (RPL) affects women's reproductive health seriously, with immune dysfunction playing a key role in its cause, yet the exact mechanisms remain elusive. We aim to investigate potential mechanisms and identify biomarkers linked to RPL. Immune cytokine testing and metabolomic profiling were conducted on the serum of 34 RPL patients and 30 healthy individuals. In the RPL group, serum interleukin-6 and interleukin-10 levels were significantly higher, while interleukin-2 and interferon-γ were significantly lower. A total of 296 differential metabolites were detected by untargeted metabolomic profiling between the RPL and control groups, with most linked to amino acid metabolism. Targeted metabolomic profiling of amino acid metabolism revealed upregulation of indole-3-acetic acid, tyrosine, glycine, isoleucine, tryptophan, lysine, aspartic acid, arginine, leucine, threonine, glutamic acid, cystine, and phenylpyruvic acid  (PPA) in the RPL group. Moreover, PPA and 5-hydroxy-L-tryptophan showed great potential in predicting RPL in a diagnostic model. Cystine and tyrosine were associated with immune cytokines in correlation analysis, suggesting potential crosstalk between amino acid metabolism and immune response in RPL. Further investigation into the molecular mechanisms underlying these findings could potentially result in the creation of novel diagnostic and therapeutic approaches for RPL.