Myclobutanil induces apoptosis and cell cycle arrest in human trophoblastic and endometrial cells through...

Myclobutanil is a triazole-based fungicide widely used in agricultural and industrial environments. Myclobutanil can persist in water and soil, affecting non-target organisms. Previous studies suggested endocrine disruption and reproductive toxicity; however, the effects on embryonic implantation were not investigated. In this study, the toxic effects of myclobutanil were assessed using human trophoblastic (HTR-8/SVneo) and uterine endometrial (T-HESCs) cell lines. Myclobutanil exposure reduced cell viability and inhibited self-aggregation ability. Furthermore, it increased the expression of apoptosis-related factors (BAX, BAK, and CASP1) and induced apoptosis. Myclobutanil also altered AKT phosphorylation and led to cell cycle arrest. In addition, myclobutanil induced reactive oxygen species (ROS) accumulation with mitochondrial membrane potential damage and Ca² ⁺ homeostasis disturbance. In particular, the genes related to trophoblastic cell mobility and endometrial receptivity were found to be aberrantly regulated. These results suggest that myclobutanil may inhibit maternal-fetal interactions and pose a risk to female reproduction.