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Protogynous fishes can change sex from female to male; concomitantly, their ovarian tissue is completely replaced by testicular tissue. The high functional conservation of gonads across organisms suggests the existence of as-yet-undefined common and essential factors in the regulation of such gonadal transformation. To identify these factors, we conducted a meta-analysis of public and newly derived gonadal transcriptome data from seven species.

Classical sex change-related genes, including cyp19a1a, foxl2, hsd17b1, amh, and gsdf, were differentially expressed between the ovary and transitional gonads, which corroborated previous reports on protogynous fishes. Moreover, we identified novel factors not previously associated with gonadal sex change in fish. Notably, the expression patterns of acetoacetyl-CoA synthetase (aacs) and apolipoprotein Eb (apoeb), which are involved in cholesterol synthesis and catabolic processes, respectively, suggest that the levels of cholesterol, a precursor of steroid hormones crucial for sex change, are decreased upon sex change onset. Thus, cholesterol dynamics may influence gonadal transformation in protogynous fishes.

This finding indicates the potential of transcriptome meta-analysis as a valuable approach to uncover previously overlooked mechanisms underlying sex change. We anticipate that further data-driven research utilizing these novel sex change-related factors will open new horizons in sex change research.