Estrogen receptors are involved in polychlorinated biphenyl-induced apoptosis on mouse spermatocyte GC-2 cell line

Area of Science:

• Environmental Toxicology
• Reproductive Biology
• Molecular Toxicology

Background:

• Polychlorinated biphenyls (PCBs) are persistent environmental contaminants with known reproductive toxicity.
• The precise molecular mechanisms underlying PCB-induced reproductive toxicity, particularly effects on spermatogenesis, remain unclear.

Purpose of the Study:

• To investigate the toxic effects of Aroclor 1254, a common PCB mixture, on spermatogenesis using a mouse cell line.
• To elucidate the molecular mechanisms by which PCBs induce reproductive toxicity, focusing on cell cycle regulation, apoptosis, and estrogen receptor signaling.

Main Methods:

• Utilized a mouse pachytene spermatocyte-derived cell line (GC-2 cells) for in vitro studies.
• Assessed the impact of Aroclor 1254 on cell proliferation, cell cycle progression (G0/G1 arrest), and apoptosis.
• Quantified the expression levels of key proteins including Bcl-2, cyclin D1, caspase-3, estrogen receptor alpha (ERα), and estrogen receptor beta (ERβ).
• Investigated the roles of ERα and ERβ using selective agonists (PPT for ERα, DPN for ERβ).

Main Results:

• Aroclor 1254 significantly inhibited GC-2 cell proliferation and induced G0/G1 cell cycle arrest and apoptosis.
• PCB treatment led to decreased Bcl-2 and cyclin D1 expression, and increased caspase-3 activation.
• Aroclor 1254 altered estrogen receptor expression, decreasing ERα and increasing ERβ.
• Selective ERα agonist PPT partially reversed PCB-induced changes, while ERβ agonist DPN exacerbated them.

Conclusions:

• Aroclor 1254 induces reproductive toxicity by disrupting spermatogenesis through mechanisms involving cell cycle arrest and apoptosis.
• Estrogen receptors ERα and ERβ play critical roles in mediating the cellular responses to PCB exposure.
• PCBs interfere with the balance between cellular apoptosis and proliferation by modulating the expression of key regulatory proteins via ER signaling pathways.