Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells

Area of Science:

• Reproductive toxicology
• Cellular biology
• Molecular mechanisms

Background:

• Cannabidiol (CBD) is a major cannabinoid in Cannabis sativa L.
• CBD is an active pharmaceutical ingredient for specific epilepsy treatments.
• CBD has demonstrated male reproductive toxicity in animal models.

Purpose of the Study:

• To identify molecular mechanisms of CBD-induced cytotoxicity in human Sertoli cells.
• To investigate CBD's effects on gene expression and cellular pathways.
• To determine if CBD induces cellular senescence.

Main Methods:

• Transcriptomic analysis using mRNA sequencing.
• Real-time PCR to confirm gene expression changes.
• Assessment of cellular senescence markers (proliferation, SA-β-gal, p16 expression).

Main Results:

• CBD significantly affected DNA replication, cell cycle, and DNA repair pathways.
• Upregulation of senescence-associated secretory phenotype (SASP) genes and p53 signaling.
• CBD induced stable cessation of proliferation and increased p16 expression, confirming cellular senescence.

Conclusions:

• CBD exposure induces cellular senescence in primary human Sertoli cells.
• CBD disrupts interrelated signaling pathways, including DNA replication and cell cycle.
• Findings highlight potential mechanisms for CBD's reproductive toxicity.