Pyrethroids and reproductive function: some endocrine disrupting perspectives from molecular simulations

Area of Science:

• Toxicology
• Molecular Biology
• Endocrinology

Background:

• Pyrethroids are widely used insecticides in agriculture and households, known for broad-spectrum efficacy and low pest resistance.
• Studies suggest human exposure to pyrethroids may lead to reproductive health issues.
• Sex hormone-binding globulin (SHBG) is crucial for regulating steroid hormone availability.

Purpose of the Study:

• To investigate the structural interactions of cypermethrin and deltamethrin with the SHBG ligand-binding pocket.
• To assess the potential of these pyrethroids to interfere with sex steroid hormone binding to SHBG.

Main Methods:

• Induced Fit Docking (IFD) was used to model pyrethroid binding to the SHBG steroid-binding pocket.
• Molecular dynamics (MD) simulations were performed on resulting SHBG-pyrethroid complexes.
• Structural analysis included molecular interactions and binding energy estimation.

Main Results:

• Both cypermethrin and deltamethrin bound tightly to the SHBG pocket, sharing common residues with the native ligand, dihydrotestosterone (DHT).
• Deltamethrin exhibited higher binding energy and greater complex stability compared to cypermethrin and DHT.
• Cypermethrin showed binding energy values close to DHT.

Conclusions:

• Deltamethrin demonstrates a stronger capability than cypermethrin to displace sex steroid hormones from SHBG.
• Both pyrethroids have the potential to interfere with sex steroid hormone transport and availability.
• This interference may consequently affect reproductive function.