Stress, novel sex genes, and epigenetic reprogramming orchestrate socially controlled sex change

Abstract

Bluehead wrasses undergo dramatic, socially cued female-to-male sex change. We apply transcriptomic and methylome approaches in this wild coral reef fish to identify the primary trigger and subsequent molecular cascade of gonadal metamorphosis. Our data suggest that the environmental stimulus is exerted via the stress axis and that repression of the aromatase gene (encoding the enzyme converting androgens to estrogens) triggers a cascaded collapse of feminizing gene expression and identifies notable sex-specific gene neofunctionalization. Furthermore, sex change involves distinct epigenetic reprogramming and an intermediate state with altered epigenetic machinery expression akin to the early developmental cells of mammals. These findings reveal at a molecular level how a normally committed developmental process remains plastic and is reversed to completely alter organ structures.

Cellular calcium and redox regulation: the mediator of vertebrate environmental sex determination?

“…Among gonochoristic (single‐sex) fish, cortisol‐mediated sex determination in response to temperature is well supported by experimental application of cortisol (Hattori et al ., ; Hayashi et al ., ; Castañeda Cortés et al ., ; Miller et al ., ). Cortisol has not yet been experimentally demonstrated to be a mediator of sex change in sequentially hermaphroditic teleost fish, but transcriptomic evidence suggests cortisol upregulation, supporting a role for the HPI axis in the repression of aromatase and the regulation of downstream epigenetic effectors of gene regulation (Fernandino et al ., ; Solomon‐Lane, Crespi & Grober, ; Goikoetxea et al ., ; Todd et al ., ).…”

“…For example, a social cue such as the removal of a dominant male induces HPI activation and glucocorticoid production in the dominant female of some species (Goikoetxea et al ., ). Elevated hormonal stress then results in aromatase repression and elevated androgen production through glucocorticoid receptor (GR) nuclear localisation and glucocorticoid receptor element (GRE) occupation in key genomic regions (Adolfi et al ., ; Todd et al ., ). Concurrently, hormonal stress leads to oxidative stress through elevated metabolism and energy production (Spiers et al ., ), and alteration in CaRe status through one or more of the mechanisms described herein.…”

“…There is variation among these species in the pattern of sex‐associated IR, perhaps arising from different ancestral genetic sex determination systems (Deveson et al ., ). In a fish that undergoes socially cued sex change, the bluehead wrasse Thalassoma bifasciatum , JARID2 and other cofactors within the PRC2 ( EZH2 , SUZ12 , EED , RNF2 ) are transiently downregulated during female to male transition (Todd et al ., ). Both JARID2 and JMJD3 also exhibit thermosensitive expression in the brains of sex‐reversed (neomale) Nile tilapia ( Oreochromis niloticus ) (Zhao et al ., ).…”

The neurogenetics of sexually dimorphic behaviors from a postdevelopmental perspective

“…38,39,44,45,[72][73][74][75][76][77][78][79] In particular, sex-specific transcripts of the downstream transcription factors doublesex (dsx) and fruitless (fru) are important for the expression of sexually dimorphic nervous systems and behaviors. 37 32,88,89 Unlike the gonad-driven sex determination in mammals we describe above, brain development in these sequential vertebrate hermaphrodites precedes gonad development and differentiation. In particular, it appears that the fru locus confers a sexual identity to developing neurons underlying adult courtship behaviors, presumably by acting as a transcriptional switch to turn on or off sexspecific patterns of gene expression that ultimately shape sex-specific neural circuits.…”

“…In particular, it appears that the fru locus confers a sexual identity to developing neurons underlying adult courtship behaviors, presumably by acting as a transcriptional switch to turn on or off sexspecific patterns of gene expression that ultimately shape sex-specific neural circuits. 32,88,92,93 Another example of a plastic sex determination system is exhibited by species with simultaneous hermaphrodites, in which male and female tissues coexist within a single individual. In fact, recent studies suggest that the regulation of both gonad and brain sex are, to some extent, decoupled in these fishes via the action of independent sex-determination epigenetic programs and gene networks in each tissue.…”