NDLI: AMPK-mTOR pathway modulates glycolysis reprogramming in unexplained recurrent spontaneous abortion

Content Provider	Springer Nature : BioMed Central
Author	Chen, Yihong Gan, Bei Zheng, Shan Zhao, Xiumei Jin, Leiyi Wei, Juanbing
Abstract	Background Recurrent spontaneous abortion (RSA), whose underlying cause has yet to be fully elucidated, is often classified as unexplained recurrent spontaneous abortion (URSA). Promoting the differentiation of CD4+ T cells into Tregs may be the key to prevent URSA. The differentiation of CD4+ T cells was controlled by mTOR, but the regulatory mechanism is still unclear. This study aims to explore the regulatory role of mTOR on CD4+ T cells and evaluate the feasibility of metformin (Met) and 2-Deoxy-D-glucose (2-DG) treatment for URSA. Methods To elucidate the mechanism of mTOR regulating Th17/Treg, transcriptome sequencing was used to analyze gene differences in clinical decidua tissue, the AMPK, mTOR and glycolytic activity in URSA mice were evaluated by RT-qPCR and WB. In addition, FCM and ELISA were also used to measure the differentiation of CD4+ T cells. Results Compared to the Control group, significant differences in gene expressions of female pregnancy and Th17 cell differentiation were observed in URSA group. Activation of AMPK and inhibition of glycolysis reduced the abortion rate in URSA mice (p = 0.0013), and inhibited CD4+ T cells differentiation to Th17 cells, which increased Treg/Th17 ratio (p < 0.001) and improved the pregnancy outcomes of URSA mice. Conclusions Our research had illustrated that AMPK-mTOR pathway regulated glycolysis reprogramming and improved the pregnancy outcomes of URSA. Furthormore, Met and 2-DG promoted the differentiation of CD4+ T cells into Treg cells, providing theoretical basis for clinical prevention of URSA.
Related Links	https://bmcpregnancychildbirth.biomedcentral.com/counter/pdf/10.1186/s12884-024-07054-1.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
ISSN	14712393
DOI	10.1186/s12884-024-07054-1
Journal	BMC Pregnancy and Childbirth
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2024-12-20
Access Restriction	Open
Subject Keyword	Reproductive Medicine Maternal and Child Health Gynecology Unexplained recurrent spontaneous abortion Glycolysis Differentiation of CD4+ T cells AMPK-mTOR pathway Treg/Th17
Content Type	Text
Resource Type	Article
Subject	Obstetrics and Gynecology
Journal Impact Factor	2.8/2023
5-Year Journal Impact Factor	3.4/2023

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Alteration of Th17 and Treg cells in patients with unexplained recurrent spontaneous abortion before and after lymphocyte immunization therapy

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AMPK-mTOR pathway modulates glycolysis reprogramming in unexplained recurrent spontaneous abortion

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