Di-n-butyl phthalate epigenetically induces reproductive toxicity via the PTEN/AKT pathway

Area of Science:

• Reproductive Toxicology
• Environmental Health
• Molecular Biology

Background:

• Di-n-butyl phthalate (DBP) is an endocrine-disrupting chemical with known adverse effects on the male reproductive system.
• The precise molecular mechanisms underlying DBP-induced germ cell toxicity are not fully understood.

Purpose of the Study:

• To elucidate the mechanism of DBP-induced toxicity in male germ cells.
• To investigate the role of the PTEN/AKT pathway in DBP's reproductive effects.

Main Methods:

• Assessing germ cell proliferation, apoptosis, and DNA damage.
• Analyzing PTEN promoter methylation and gene expression.
• Investigating the interaction between miR-29b, DNMT3b, and PTEN methylation.
• Evaluating AKT pathway signaling and sperm parameters.

Main Results:

• DBP exposure led to reduced germ cell proliferation, increased apoptosis, and DNA damage.
• DBP decreased PTEN promoter methylation, increasing PTEN expression and inhibiting the AKT pathway.
• miR-29b was identified as a regulator of DNMT3b, influencing PTEN methylation.
• Reduced sperm count, motility, and progression were linked to AKT pathway downregulation and affected sperm flagellum genes.

Conclusions:

• DBP induces male reproductive toxicity by causing aberrant PTEN demethylation.
• Inhibition of the AKT pathway, driven by increased PTEN expression, is a key mechanism in DBP's toxicity.
• These findings highlight the role of epigenetic modifications and signaling pathway disruption in phthalate-induced reproductive harm.