Aromatase, brain sexualization and plasticity: the fish paradigm

Abstract

In contrast to mammals, teleost fish have a very labile genetic sex determination. Sex differentiation is influenced by a combination of hormonal, social and environmental factors and teleost fishes exhibit many examples of hermaphroditism. This means that the brain of fish is not irreversibly sexualized early in life. This review aims at highlighting some unique features of fish that may explain their brain sexual plasticity. Unlike mammals, in which brain aromatase activity decreases after birth, adult teleosts exhibit an intense aromatase activity due to strong expression of one of two aromatase genes (aromatase A or cyp19a1a and aromatase B or cyp19a1b) that arose from a gene duplication event. Interestingly, aromatase B is only expressed in radial glial cells (RGC) of adult fish. These cells persist throughout life and act as progenitors in the brain of both developing and adult fish. In agreement with the fact that brain aromatase activity is correlated with sex steroid levels, the high expression of cyp19a1b is due to an autoregulatory loop through which estrogens and aromatizable androgens upregulate aromatase expression. Given the well-established roles of estrogens and aromatase on brain sexualization, these features suggest that the brain of fish conserves properties of embryonic mammalian brain throughout life - high neurogenic activity and high aromatase expression in progenitor cells correlated with sex steroid levels. The permanent dialogue between the brain and the gonad would permit sex changes and thus the emergence of a variety of reproductive strategies. Other hypotheses are also discussed.

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

“…In fishes, the brain remains active in sex steroid production in the adult stage and is supposedly interacting with the gonad [Le Page et al, 2010]. This becomes evident during sex change in hermaphrodites, which is accompanied by changes in aromatase gene expression in the brain [Breton et al, 2015].…”

Climate change and pollution speed declines in zebrafish populations

“…Furthermore, the scope for directional selection to maintain sex ratios in species exhibiting environmental sex determination during climate change (76, 77) is likely to diminish, because temperature fluctuations are predicted to increase along with mean global temperatures (50). Therefore, more immediate phenotypic responses are likely to be of greater importance, including population dynamic responses buffering recruitment (as illustrated in our sensitivity analysis) and phenotypic plasticity in sexual development (78). Due to its rapid life cycle, sexual plasticity as a juvenile, and potential to undergo sex change during adulthood (78), although not proven (79), the zebrafish would appear to be a sensitive model for illustrating the potential impacts of climate change.…”

The Reversible Sex of Gonochoristic Fish: Insights and Consequences

“…In contrast, brain sex differentiation in birds and mammals occurs only during embryo development and is shown to be mediated not only by gonadal steroids but also by genes on the sex chromosomes as well as epigenetic regulations [McCarthy and Arnold, 2011]. Several neurosteroids are produced in the teleost brain, notably estrogen with an extremely elevated aromatase activity that increases with age, probably for the continuous neurogenesis [Le Page et al, 2010]. Most teleosts possess 2 aromatase genes (cyp19a1a and cyp19a1b) generated during teleost genome duplication, with cyp19a1b being the predominant brain gene [Le Page et al, 2010].…”

“…Several neurosteroids are produced in the teleost brain, notably estrogen with an extremely elevated aromatase activity that increases with age, probably for the continuous neurogenesis [Le Page et al, 2010]. Most teleosts possess 2 aromatase genes (cyp19a1a and cyp19a1b) generated during teleost genome duplication, with cyp19a1b being the predominant brain gene [Le Page et al, 2010]. The cyp19a1b gene is thought to be implicated in a feedback loop in the brain regulating teleost steroid production through the kisspeptin and the hypothalamo-pituitarygonadal axis [Hofmann, 2006].…”