How mTOR and AMPK signals relate to placental problems and preeclampsia, and how metformin may help

Preeclampsia is associated with a shift towards increased AMPK activation and reduced mTORC1 activity in the placenta.

• The physiological balance between mTORC1 and AMPK is crucial for proper trophoblast invasion and nutrition during normal pregnancy.
• Chronic placental hypoxia and oxidative stress in preeclampsia disrupt this balance, leading to adverse effects on trophoblast function.
• Increased anti-angiogenic factor production is a consequence of the altered mTOR/AMPK interaction in preeclampsia.
• Low doses of AMPK activation may help restore metabolic balance, but higher doses, particularly with metformin, could further inhibit mTORC1 activity.
• Targeting the mTOR/AMPK axis offers insights into preeclampsia mechanisms and potential therapies, although careful dosing of metformin is necessary.

Simplified