Pendimethalin exposure disrupts mitochondrial function and impairs processes related to implantation

Area of Science:

• Agricultural Science
• Toxicology
• Cell Biology

Background:

• Pendimethalin (PDM) is a widely used dinitroaniline herbicide in agriculture.
• While PDM is known to cause reproductive issues, its specific toxicity mechanisms during the pre-implantation stage remain unclear.

Purpose of the Study:

• To investigate the effects of PDM on porcine trophectoderm (pTr) and uterine luminal epithelial (pLE) cells.
• To elucidate the cellular and molecular mechanisms underlying PDM-induced toxicity in the pre-implantation phase.

Main Methods:

• Assessed PDM's impact on cell proliferation, intracellular reactive oxygen species (ROS) generation, and calcium (Ca2+) homeostasis in pTr and pLE cells.
• Investigated mitochondrial membrane potential, Ca2+ influx into mitochondria, and the mitogen-activated protein kinase (MAPK) signaling pathway.
• Evaluated cell cycle progression, programmed cell death, cell migration, and the expression of implantation-related genes.

Main Results:

• PDM exposure induced anti-proliferative effects, increased intracellular ROS, and caused excessive Ca2+ influx into mitochondria.
• Mitochondrial dysfunction and disrupted Ca2+ homeostasis were observed, leading to cell cycle arrest and programmed cell death.
• PDM exposure decreased cell migration and dysregulated the expression of key genes involved in pTr and pLE cell function.

Conclusions:

• PDM exposure triggers significant cellular damage, including mitochondrial dysfunction and disrupted Ca2+ homeostasis, in porcine reproductive cells.
• These cellular disruptions result in impaired cell proliferation, migration, and survival, indicating potential adverse effects on the implantation process.
• This study provides novel insights into the detailed mechanism of PDM toxicity, highlighting its potential risks to reproductive health in pigs.