Ethalfluralin impairs implantation by aggravation of mitochondrial viability and function during early pregnancy

Abstract

Ethalfluralin, a dinitroaniline-type herbicide, has been used for decades. As a result, its residues are detected on some farmlands. To determine the molecular mechanisms underlying the detrimental effects of ethalfluralin on early pregnancy, porcine luminal epithelium and trophectoderm cell lines were used. Ethalfluralin was found to inhibit the viability, proliferation, and migration of porcine luminal epithelial (pLE) and porcine trophectoderm (pTr) cells. Additionally, ethalfluralin induced apoptotic cell death by means of an imbalance in calcium homeostasis in both pLE and pTr cells. Ethalfluralin decreased mitochondrial membrane potential (Delta Psi m) and impaired mitochondrial respiration by downregulating the mitochondrial respiratory complex-related genes. Ethalfluralin also activated endoplasmic reticulum stress signals and autophagy pathways, increased the phosphorylation of P38 MAPK and NF-Kappa B, and suppressed the PI3K/AKT signaling pathway. Taken together, this study elucidated the molecular mechanisms by which ethalfluralin impedes the viability and mitochondrial function in fetal trophectoderm and maternal endometrial cells during early pregnancy.