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

Autor: Chen Y; Department of Obstetrics and Gynecology, The First Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, Fujian, 350005, P.R. China., Gan B; Department of Obstetrics and Gynecology, The First Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, Fujian, 350005, P.R. China., Zheng S; Department of Obstetrics and Gynecology, The First Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, Fujian, 350005, P.R. China., Zhao X; Department of Obstetrics and Gynecology, The First Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, Fujian, 350005, P.R. China., Jin L; Department of Obstetrics and Gynecology, The First Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, Fujian, 350005, P.R. China., Wei J; Department of Obstetrics and Gynecology, The First Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, Fujian, 350005, P.R. China. weijuanbing@126.com.
Jazyk: angličtina
Zdroj: BMC pregnancy and childbirth [BMC Pregnancy Childbirth] 2024 Dec 20; Vol. 24 (1), pp. 840. Date of Electronic Publication: 2024 Dec 20.
DOI: 10.1186/s12884-024-07054-1
Abstrakt: 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.
Competing Interests: Declarations. Ethics approval and consent to participate: All participants provided informed consent, and the human subject protocol used in this study has been approved by the Ethics Committee of Fujian Medical University Clinical Research (No. [2023]075). The study complies with the Regulations on the Management of Experimental Animals approved by the State Council of the People’s Republic of China, with the approval from Laboratory Animal Committee of Fujian Medical University (IACUC FJMU 2023-Y-0524). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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