Aclonifen is a diphenyl-ether herbicide that is used to control the growth of weeds while growing crops such as corn and wheat. Although the biochemical effects of aclonifen are well characterized, including its ability to inhibit protoporphyrinogen oxidase and carotenoid synthesis, the toxicity of aclonifen in embryonic implantation and development during early pregnancy, has not been reported. Thus, in this study, we investigated the potential interference of aclonifen in embryonic implantation using porcine trophectoderm (pTr) and uterine luminal epithelial (pLE) cells isolated during implantation period of early pregnancy. Cell viability in both pTr and pLE cells significantly decreased in a dose-dependent manner following aclonifen treatment. Moreover, the proportion of cells in the sub-G1 phase of the cell cycle gradually increased upon treatment with increasing concentrations of aclonifen, which in turn led to an increase in the number of apoptotic cells, as determined by annexin V and propidium iodide staining. Aclonifen treatment caused mitochondrial dysfunction by increasing the depolarization of the mitochondrial membrane potential and the mitochondrial calcium concentration. Aclonifen inhibited cell mobility by suppressing the expression of implantation-related genes in pTr and pLE cells. To explore the underlying mechanism, we evaluated the phosphorylation of PI3K and MAPK signaling molecules. The phosphorylation of AKT, S6, JNK, and ERK1/2 were significantly increased by aclonifen. Collectively, our results suggest that aclonifen may interrupt implantation during early pregnancy by disrupting maternal–fetal interaction.
Bibliographical noteFunding Information:
This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (grant number: 2021R1A2C2005841 & 2021R1C1C1009807 ). Also, this research was supported by development of living shoreline technology based on blue carbon science toward climate change adaptation of Korea Institute of Marine Science & Technology Promotion (KIMST) funded by the Ministry of Oceans and Fisheries ( KIMST-20220526 ).
© 2022 Elsevier Inc.
- Cell death
- Porcine trophectoderm
- Uterine luminal epithelial cell
ASJC Scopus subject areas
- Agronomy and Crop Science
- Health, Toxicology and Mutagenesis