Multiple transcriptomic profiling: potential novel metabolism-related genes predict prepubertal testis damage caused...

Area of Science:

• Toxicology
• Reproductive Biology
• Molecular Biology

Background:

• Di(2-ethylhexyl) phthalate (DEHP) is an endocrine-disrupting chemical with known reproductive toxicity.
• Prepubertal testicular development is particularly sensitive to environmental toxicants.
• Understanding DEHP's specific effects on the developing male reproductive system is crucial for risk assessment.

Purpose of the Study:

• To investigate the toxic effects of various di(2-ethylhexyl) phthalate (DEHP) doses on prepubertal mouse testes.
• To identify molecular mechanisms and biomarkers associated with DEHP-induced testicular damage.
• To evaluate DEHP's impact on reproductive processes and gene expression in developing male mice.

Main Methods:

• Male mice (3 weeks old) were administered different doses of DEHP (4.8 to 500 mg/kg/day) via gavage.
• Evaluated testicular organ coefficient, spermatogenic epithelium, and serum testosterone levels.
• Utilized ribonucleic acid sequencing (RNA-seq) for gene expression analysis and pathway enrichment (Gene Ontology, Reactome).

Main Results:

• Significant abnormalities in testicular organ coefficient, spermatogenic epithelium, and testosterone were observed in the highest DEHP dose group (500 mg/kg/day).
• RNA-seq analysis revealed enrichment of reproduction and metabolism pathways in DEHP-exposed groups.
• Common gene analysis indicated similar damage patterns in the prepubertal testis across a range of DEHP exposure levels (4.8 to 500 mg/kg/day).

Conclusions:

• DEHP exposure significantly impacts prepubertal testicular function and reproductive health.
• Fatty acid binding protein 3 (Fabp3) and carboxylesterase 1d (Ces1d) were identified as key transcriptional biomarkers for DEHP-induced testicular injury.
• These findings offer insights into DEHP's gene regulatory mechanisms and aid in predicting and diagnosing prepubertal testicular damage.