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Placenta · 2026

The AMPK/mTOR axis is linked to placental ferroptosis in human gestational diabetes mellitus.

СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Li Qian, Yin Xiaoyi, Guo Ziyi, Zhao Haobin, Li Niannian, Zhu Yuchun, Wang Guanglei

Аннотация

BACKGROUND: Ferroptosis has been closely implicated in placenta-related complications. Nevertheless, its specific role in the placenta of gestational diabetes mellitus (GDM) remains poorly understood. We hypothesized that ferroptosis contributes to impaired placental cell function in GDM and that the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) axis acts as an potential regulator of ferroptosis.

METHODS: Term placental tissues from pregnant women with GDM and healthy controls were analyzed, and the human chorionic trophoblast line (HTR8/SVneo) was used in the in vitro experiments.

RESULTS: Altered levels of ferroptosis markers-transferrin receptor 1 (TfR1), acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), ferrous iron and malondialdehyde (MDA), and potential ferroptosis mediators-reactive oxygen species (ROS), AMPK, and mTOR were observed in GDM placentas compared to control. AMPK inhibitor, AMPK activator, and mTOR inhibitor were applied to modulate the AMPK/mTOR signaling axis in in vitro experiments. Our in vitro data revealed that modulation of AMPK or mTOR activation directly affects the induction of ferroptosis as well as trophoblast cell proliferation and migration.

CONCLUSIONS: Our study suggests that AMPK/mTOR axis is closely associated with placental ferroptosis which may represent a promising therapeutic target for mitigating GDM-related placental complications following further validation in animal models.

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

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