# Zearalenone Promotes Uterine Hypertrophy through AMPK/mTOR Mediated Autophagy

## TL;DR

Zearalenone causes uterine growth in piglets by activating AMPK/mTOR pathways and promoting cell proliferation.

## Contribution

This study reveals a novel mechanism by which ZEN induces uterine hypertrophy through AMPK/mTOR-mediated autophagy.

## Key findings

- ZEN activates AMPK phosphorylation in uterine cells, influencing mTOR via TSC2 and Rheb.
- ZEN upregulates PCNA and BCL2 while downregulating BAX, promoting cell proliferation and uterine hypertrophy.

## Abstract

Zearalenone (ZEN), a non-steroidal Fusarium graminearum with an estrogen effect, can cause damage to the gastrointestinal tract, immune organs, liver, and reproductive system. Further analysis of the mechanism of ZEN has become an important scientific issue. We have established in vivo and in vitro models of ZEN intervention, used AMPK/mTOR as a targeted pathway for ZEN reproductive toxicity, and explored the molecular mechanism by which ZEN may induce uterine hypertrophy in weaned piglets. Our study strongly suggested that ZEN can activate the phosphorylation of AMPK in uterine endometrial epithelium cells, affect the phosphorylation level of mTOR through TSC2 and Rheb, induce autophagy, upregulate the expression of proliferative genes PCNA and BCL2, downregulate the expression of apoptotic gene BAX, promote uterine endometrial epithelium cells proliferation, and ultimately lead to thickening of the endometrial and myometrium, increased density of uterine glands, and induce uterine hypertrophy.