Gadolinium induces Sertoli cell damage: cellular and molecular mechanisms

Area of Science:

• Environmental toxicology
• Reproductive toxicology
• Cell biology

Background:

• Gadolinium (Gd) is widely used in industry and medicine, raising environmental concerns.
• Gd's persistence in water and soil allows entry into the human food chain.
• Gd's toxic effects on male reproductive health, particularly Sertoli cells, are largely unknown.

Purpose of the Study:

• To investigate the toxic effects of gadolinium on mouse TM4 Sertoli cells.
• To elucidate the cellular and molecular mechanisms underlying Gd toxicity in Sertoli cells.

Main Methods:

• Exposure of mouse TM4 Sertoli cells to varying concentrations of GdCl₃ or Gd₂O₃ for 24 hours.
• Evaluation of cellular responses including viability, proliferation, oxidative stress, and protein expression.
• Assessment of molecular changes in mitochondrial function, junctional proteins, and cell death pathways.

Main Results:

• Gd exposure induced oxidative stress, reduced cell viability, and inhibited proliferation in TM4 cells.
• Gd suppressed androgen receptor protein expression and lactate dehydrogenase (LDH) activity.
• Gd decreased junctional protein expression, particularly Gd₂O₃, and activated autophagic and apoptotic processes.
• Mitochondrial impairment and altered Mitochondria-Associated Membranes were observed.

Conclusions:

• Sertoli cells are identified as targets of gadolinium toxicity.
• Gd exposure disrupts Sertoli cell function, impacting male reproductive health.
• The findings provide a new understanding of Gd's reproductive risks.