# Sex-Specific Molecular and Genomic Responses to Endocrine Disruptors in Aquatic Species: The Central Role of Vitellogenin

## TL;DR

This paper reviews how endocrine disruptors affect aquatic species, focusing on vitellogenin and its role in hormonal and reproductive changes.

## Contribution

The paper highlights the integration of vitellogenin with multi-omics data to understand sex-specific responses to endocrine disruptors.

## Key findings

- Vitellogenin induction is part of broader transcriptional networks involving genes like cyp19a1 and cyp1a.
- Epigenetic mechanisms like DNA methylation and microRNAs modulate sex-dependent sensitivity to endocrine disruptors.
- Integrating VTG with transcriptomic and epigenetic data supports mechanistic understanding of reproductive impairment.

## Abstract

Endocrine-disrupting chemicals (EDCs) are widespread contaminants that interfere with hormonal signaling and compromise reproductive success in aquatic organisms. Vitellogenin (VTG) is one of the most widely established biomarkers of estrogenic exposure, especially in males and juveniles. However, evidence from multi-omics studies indicates that VTG induction occurs within broader transcriptional and regulatory networks, involving genes such as cyp19a1 (aromatase), cyp1a (cytochrome P4501A), and other stress-responsive genes, underscoring the complexity of endocrine disruption. This review focuses on nuclear receptor isoforms, including estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and androgen receptor (AR) variants. We examine the diversification of vtg gene repertoires across teleost genomes and epigenetic mechanisms, such as DNA methylation and microRNAs, that modulate sex-dependent sensitivity. In addition, we discuss integrative approaches that combine VTG with transcriptomic, epigenetic, and histological endpoints. Within the Adverse Outcome Pathway (AOP) and weight-of-evidence (WoE) frameworks, these strategies provide mechanistic links between receptor activation and reproductive impairment. Finally, we outline future directions, focusing on the development of sex-specific biomarker panels, the integration of omics-based data with machine learning, and advances in ecogenomics. Embedding molecular responses into ecological and regulatory contexts will help bridge mechanistic insights with environmental relevance and support sustainability goals such as SDG 14 (Life Below Water).