Copper Pyrithione Inhibits Trophoblast Cell Function: Mechanisms Underlying Its Embryotoxic Potential

Area of Science:

• Reproductive Toxicology
• Cell Biology
• Molecular Mechanisms

Background:

• Copper pyrithione (CuPT) is a common antimicrobial in antifouling coatings and consumer products.
• CuPT exhibits potential reproductive toxicity, necessitating further investigation into its cellular effects.

Purpose of the Study:

• To evaluate the impact of CuPT on human trophoblast-like JEG-3 cells.
• To elucidate the molecular mechanisms underlying CuPT-induced toxicity in JEG-3 cells.

Main Methods:

• JEG-3 cells were treated with CuPT, and effects on proliferation, migration, invasion, cell cycle, and apoptosis were assessed.
• Intracellular reactive oxygen species (ROS) and DNA double-strand breaks were measured.
• Transcriptomic changes were analyzed using RNA-sequencing, and autophagy and ER stress markers were evaluated via immunofluorescence.
• Key gene expressions were validated using qRT-PCR.

Main Results:

• CuPT inhibited JEG-3 cell proliferation, migration, and invasion in a dose- and time-dependent manner.
• CuPT exposure led to increased ROS levels, oxidative stress, DNA damage (elevated γ-H2AX foci), and late apoptosis.
• RNA-seq revealed significant alterations in gene expression, with enrichment of ER stress, unfolded protein response, apoptosis, and autophagy pathways.
• CuPT induced autophagosome formation and ER stress, downregulating CYTB, ND6, Egln3 and upregulating NUPR1, SQSTM1.

Conclusions:

• CuPT adversely affects trophoblast-like JEG-3 cell function, impairing proliferation, migration, and invasion.
• The toxicity mechanisms involve oxidative stress, DNA damage, ER stress activation, and autophagy induction.
• These findings highlight the reproductive toxicity risks associated with CuPT exposure.