Bone Marrow Mesenchymal Stem Cells (BMSCs) Enhance the In Vitro Activities of Endometrial Cells via Strengthening the Phosphorylation and Activation of Phosphoinositide 3-Kinase (PI3K)

Abstract

Mancozeb (ethylene bis-dithiocarbamate) is an organometallic fungicide and is widely used in agriculture and is related to women’s spontaneous abortion and menstrual abnormalities. Bone marrow mesenchymal stem cells (BMSCs) can impede endometrial fibrosis via suppressing PI3K pathway, but its effect on the activity of endometrial cells induced by mancozeb/EDU is unclear. This study intends to explore the protective effects of co-culture with BMSCs on endometrial cells after mancozeb/EDU treatment. Endometrial cells were randomized into control group, mancozeb/EDU group (mancozeb/EDU treatment), BMSCs group (cells were co-cultured with BMSCs after mancozeb/EDU treatment), and inhibitor group (treated with PI3K-Akt-mTOR inhibitor) followed by analysis of the expression of PI3K-Akt-mTOR pathway-related proteins, cell viability by MTT and cell invasion and migration by Transwell and scratch test. Mancozeb/EDU treatment significantly inhibited PI3K-Akt-mTOR signals and cell proliferation, increased apoptosis and decreased cell invasion and migration, which were all reversed by co-culture with BMSCs. Additionally, the co-culture with BMSCs modulated the In Vitro viability of endometrial cells by influencing PI3K-Akt-mTOR signal transduction pathway, which can be inverted by PI3K-Akt-mTOR pathway-specific antagonists. In conclusion, BMSCs exerted a protective effect on the In Vitro viability of endometrial cells by manipulating the PI3K/Akt/mTOR signal transduction, which helped to protect endometrial cells from damage caused by mancozeb/ETU treatment.