Cell migration and adhesion in autophagy-induced damage of human trophoblast cells.

INTRODUCTION

Intrahepatic cholestasis of pregnancy (ICP) is a common pregnancy complication. It has relatively minor impacts on the mother, but elevated bile acid levels pose severe risks to the fetus, potentially causing adverse pregnancy outcomes such as preterm birth, intrauterine distress, and fetal death. Autophagy plays a pivotal role in embryonic development, implantation, and pregnancy maintenance. Emerging evidence indicates autophagy is involved in ICP, yet its underlying mechanism remains unclear.

METHODS

An ICP-associated autophagy-impaired cell model was established. This was achieved by treating human HTR-8/SVneo trophoblast cells with high-concentration bile acids and culturing the cells under starvation conditions.

RESULTS

The induced autophagic impairment significantly reduced placental cell migration, adhesion, and proliferation. This effect was mediated by inhibiting the extracellular matrix (ECM) and focal adhesion (FA) pathways, while also promoting cell apoptosis. Gene expression analysis revealed a regulatory connection between the autophagic pathway and key molecules-including ECM, integrins, and actin-which are critical for placental development and functional maintenance.

DISCUSSION: This study provides novel theoretical insights into the pathogenesis of ICP. It proposes that the dysregulation of FAs and ECM by autophagy is a key mechanism underlying ICP-associated adverse pregnancy outcomes.