# Integrated application of transcriptomics and metabolomics provides insights into gonadal differentiation in Mesocentrotus nudus

## TL;DR

This study explores how sea urchins develop male or female gonads by combining gene and metabolite data, revealing key pathways and potential markers for sex differentiation.

## Contribution

The study provides novel molecular insights into sex differentiation in sea urchins through integrated transcriptomic and metabolomic analyses.

## Key findings

- Sex-specific amino acid levels suggest metabolic differences between ovaries and testes in M. nudus.
- Key genes like GATA4 and CYP17A1 are potential markers for gonadal differentiation.
- TGF-β signaling and retinol metabolism genes show sex-biased expression during differentiation.

## Abstract

Mesocentrotus nudus is an important aquaculture species in East Asia, valued for its gonads as the only edible part. However, the molecular basis of gonadal differentiation in this species remains poorly understood. In this study, we determined that morphological gonadal differentiation occurs when individuals reach a test diameter of approximately 40 mm. Amino acid profiling revealed sex-specific differences between ovaries and testes, with higher levels of lysine, proline, alanine, and glutamic acid in testes, suggesting sexual dimorphism in metabolic demand. To investigate the regulatory mechanisms involved, we conducted integrated transcriptomic and metabolomic analyses between differentiated and undifferentiated gonads. Differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs) including retinoic acid, linoleic acid, and arachidonic acid, were significantly enriched in retinol metabolism, steroid biosynthesis, and amino acid metabolic pathways. Several key genes, such as GATA4, CYP17A1, and HSD17B, were identified as potential markers for gonadal differentiation. Furthermore, components of the TGF-β signaling pathway (Smads, Rbx1, SKP) and retinol metabolism genes (CYP26, CYP1A, CYP3A) exhibited sex-biased expression patterns. This study provides novel insights into the molecular mechanisms underlying sex differentiation in sea urchins and lays a molecular foundation for the development of sex-control breeding strategies.

The online version contains supplementary material available at 10.1038/s41598-025-32582-x.