Pregnane X receptor attenuates gold nanoparticles' toxicity through accelerating zebrafish embryo hatching

Area of Science:

• Environmental Toxicology
• Molecular Biology
• Developmental Biology

Background:

• Fish embryos are sensitive to waterborne nanoparticles (NPs), with delayed hatching as a key indicator.
• Hatching enzymes (HEs) are thought to detoxify NPs, but the underlying molecular mechanisms are unclear.

Purpose of the Study:

• To investigate the role of pregnane X receptor (Pxr) in zebrafish embryo hatching following gold nanoparticle (AuNP) exposure.
• To elucidate the mechanism by which AuNPs affect embryo hatching and detoxification.

Main Methods:

• Zebrafish embryos (Danio rerio) were exposed to 4 nm and 82 nm AuNPs at various developmental stages.
• Pxr knockout and inhibition were employed to assess its role in hatching and HE expression.
• RNA sequencing was used to analyze gene expression changes in response to AuNPs and Pxr manipulation.
• Locomotor activity of zebrafish larvae was assessed.

Main Results:

• Both 4 nm and 82 nm AuNPs inhibited zebrafish embryo hatching, with smaller AuNPs being more toxic.
• AuNPs induced mRNA expression of HEs and Pxr at non-toxic and EC50 concentrations.
• Pxr deficiency or inhibition reduced HE induction by AuNPs and significantly delayed hatching.
• Pxr activation accelerated hatching, correlating with HE activity and influencing muscle development and energy metabolism.

Conclusions:

• Pregnane X receptor (Pxr) plays a crucial role in promoting zebrafish embryo hatching and contributes to the detoxification of gold nanoparticles (AuNPs).
• Pxr's influence extends to muscle development and energy metabolism, affecting embryo motility and hatching efficiency.