Transcriptomic Changes Across the HPG Axis Following Prenatal Exposure to the EDC Mixture NeuroMix

Area of Science:

• Endocrinology
• Toxicology
• Genomics

Background:

• Endocrine-disrupting chemicals (EDCs) are widespread environmental contaminants.
• Previous research showed prenatal EDC exposure alters rat physiology and behavior.
• The molecular mechanisms underlying these EDC-induced changes remain largely unknown.

Purpose of the Study:

• To investigate the molecular mechanisms of prenatal EDC exposure on the hypothalamic-pituitary-gonadal (HPG) axis.
• To identify sex-specific gene expression changes in response to the EDC mixture NeuroMix (NMX).

Main Methods:

• Utilized 3' Tag-based RNA sequencing (TagSeq) on HPG tissues from male and female rats prenatally exposed to NMX.
• Performed Gene Ontology (GO) enrichment analysis to identify affected biological pathways.
• Analyzed pathway activation using Qiagen Ingenuity Pathway Analysis.

Main Results:

• Prenatal NMX exposure induced significant, sex-specific differentially expressed genes (DEGs) across HPG tissues.
• In males, the hypothalamic arcuate nucleus (ARC) showed 613 DEGs, with affected genes related to synaptic plasticity and hormone response.
• In females, ovaries exhibited 1295 DEGs, with altered genes involved in ciliary function and immune processes.

Conclusions:

• Prenatal exposure to the EDC mixture NMX impacts gene expression across the HPG axis in a sex-dependent manner.
• These findings highlight the potential for EDCs to disrupt reproductive health through molecular alterations.
• This study provides novel transcriptomic insights into EDC effects on the HPG axis.