Sexually Dimorphic and Intersex-Specific Transcriptional Responses in Cherax quadricarinatus Hepatopancreas Following Methyl Farnesoate Exposure

The redclaw crayfish (Cherax quadricarinatus) features a unique intersex phenotype—functional males harboring a female (ZW) genotype. This study investigates the sexually dimorphic transcriptomic responses of the hepatopancreas to acute methyl farnesoate exposure to decouple genotypic from phenotypic sex. We found that normal males prioritize enzymatic detoxification and steroidogenesis, whereas normal females prioritize energy conservation for reproductive preparation. Strikingly, intersex individuals exhibited a massive transcriptomic burst and paradoxical hormone receptor dynamics, exposing a fragile endocrine network driven by their inherent genotypic–phenotypic conflict. To survive severe MF-induced pharmacological stress, the intersex hepatopancreas actively suppresses lysosomal and apoptotic pathways, which we hypothesize serves as a compensatory mechanism to mitigate severe tissue damage. Instead, it deploys a compensatory architecture by hyperactivating amino acid biosynthesis, sulfur relay systems, and gap junctions to manage proteotoxic and oxidative stress. Co-expression network analysis identified VCP, maf, and hdac8 as central regulatory hubs orchestrating this survival strategy through proteostasis, oxidative sensing, and epigenetic override. These findings suggest that the crustacean response to acute pharmacological challenge involves profound metabolic and epigenetic reprogramming, providing novel hypotheses for future functional studies.