Inhibition of Aromatase Induces Partial Sex Change in a Cichlid Fish: Distinct Functions for Sex Steroids in Brains and Gonads

Abstract

Sex steroids are major drivers of sexual development and also responsible for the maintenance of the established gender. Especially fishes exhibit great plasticity and less conservation in sex determination and sexual development compared to other vertebrate groups. In addition, fishes have a constant sex steroid production throughout their entire lifespan, which makes them particularly susceptible to interferences with the endogenous sex steroid system. This susceptibility has recently been used to show that inhibition of the key enzyme of estrogen synthesis, aromatase Cyp19a1, can induce functional sex reversal even in adult fish. Here, we investigated the impact of the aromatase inhibitor (AI) fadrozole in adult females of the East African cichlid fish Astatotilapia burtoni. Using gene expression, phenotypic measurements, behavioral experiments, and hormone measurements, we assessed if females treated with fadrozole develop a male-like phenotype. We found that AI treatment has a different effect on gene expression in the gonad compared to the brain, the 2 tissues mostly implicated in sexual development. In contrast to observations in other gonochoristic species, A. burtoni ovaries cannot be transformed into functional testis by AI. However, rapid changes towards a male-like phenotype can be induced with AI in coloration, hormone levels, and behavior.

The Reversible Sex of Gonochoristic Fish: Insights and Consequences

“…All the hormonal sex reversal treatments that have since been applied to numerous fish species are based upon these pioneer studies. As reported by Göppert et al [2016], this plasticity of sex differentiation can also lead to xenobiotic-induced sex reversal in fish due to pollution. Since these endocrine disrupting effects have been recently reviewed Senthilkumaran, 2015], they will not be discussed further in the present review.…”

“…AI treatment of the African cichlid Astatotilapia burtoni adult females did not cause sex reversal of the ovaries retaining female gene profiles; however, partial masculinization was observed with changes in coloration, body shape and form, steroid levels, and notably modifications in the brain gene expressions which affected sexual behavior [Göppert et al, 2016]. Cyp19a1a present in the brain in this species was upregulated in AI females while both arα and cyp19a1b were downregulated, resembling the profiles of males which could be to compensate E2 levels or due to higher testosterone levels.…”

Variations on a theme: Genomics of sex determination in the cichlid fish Astatotilapia burtoni

“…Other explanations are that sex reversal [23] or intersex individuals can occur in our lab strain (we occasionally observed individuals that had a male phenotype but lay eggs as well as one intersex individual with a mixed gonad, A. Böhne and B. Egger, personal observations). Sex reversal can counteract Muller’s ratchet by purging deleterious mutations through occasional recombination in XY females, which results in rejuvenating sex chromosomes, preventing them from strong differentiation and decay and thus accounting for homomorphic sex chromosomes [60, 61].…”

“…Fish were kept at the aquarium facilities of the Zoological Institute of the University of Basel under standard conditions [23]. A male-female pair of the reference lab strain of A. burtoni (inbred line) as well as a male-female pair of A. burtoni caught at the estuary of the Kalambo river in LT at Chipwa village (Additional file 1: Figure S1) were crossed.…”

Non‐canonical expression patterns and evolutionary rates of sex‐biased genes in a seasonal fish

“…The male‐biased expression of cyp19a1a , which encodes the key enzyme of gonadal estrogen production, was unexpected because aromatase inhibition induces female‐to‐male sex change in the adult cyprinid zebrafish (Takatsu et al, ) and partial sex change in the adult African cichlid Astatotilapia burtoni (Göppert et al, ). On the other hand, these data are in line with the male‐biased expression of cyp19a1a in the African cichlid Ophthalmotilapia ventralis (Böhne et al, ), in which gonadal aromatase accumulates with the overexpression of esr2b (Böhne et al, ).…”