Female Mimicry by Sneaker Males Has a Transcriptomic Signature in Both the Brain and the Gonad in a Sex-Changing Fish.

Phenotypic plasticity represents an elegant adaptive response of individuals to a change in their environment. Bluehead wrasses (Thalassoma bifasciatum) exhibit astonishing sexual plasticity, including female-to-male sex change and discrete male morphs that differ strikingly in behavior, morphology, and gonadal investment. Using RNA-seq transcriptome profiling, we examined the genes and physiological pathways underlying flexible behavioral and gonadal differences among female, dominant (bourgeois) male, and female-mimic (sneaker) male blueheads. For the first time in any organism, we find that female mimicry by sneaker males has a transcriptional signature in both the brain and the gonad. Sneaker males shared striking similarity in neural gene expression with females, supporting the idea that males with alternative reproductive phenotypes have "female-like brains." Sneaker males also overexpressed neuroplasticity genes, suggesting that their opportunistic reproductive strategy requires a heightened capacity for neuroplasticity. Bourgeois males overexpressed genes associated with socio-sexual behaviors (e.g., isotocin), but also neuroprotective genes and biomarkers of oxidative stress and aging, indicating a hitherto unexplored cost to these males of attaining the reproductively privileged position at the top of the social hierarchy. Our novel comparison of testicular transcriptomes in a fish with male sexual polymorphism associates greater gonadal investment by sneaker males with overexpression of genes involved in cell proliferation and sperm quality control. We propose that morphological female-mimicry by sneaker male teleosts entails pervasive downregulation of androgenesis genes, consistent with low androgen production in males lacking well-developed secondary sexual characters.

Estrogenic signaling and sociosexual behavior in wild sex-changing bluehead wrasses, Thalassoma bifasciatum.

Estrogenic signaling is an important focus in studies of gonadal and brain sexual differentiation in fishes and vertebrates generally. This study examined variation in estrogenic signaling (1) across three sexual phenotypes (female, female-mimic initial phase [IP] male, and terminal phase [TP] male), (2) during socially-controlled female-to-male sex change, and (3) during tidally-driven spawning cycles in the protogynous bluehead wrasse (Thalassoma bifasciatum). We analyzed relative abundances of messenger RNAs (mRNAs) for the brain form of aromatase (cyp19a1b) and the three nuclear estrogen receptors (ER) (ERα, ERßa, and ERßb) by qPCR. Consistent with previous reports, forebrain/midbrain cyp19a1b was highest in females, significantly lower in TP males, and lowest in IP males. By contrast, ERα and ERßb mRNA abundances were highest in TP males and increased during sex change. ERßa mRNA did not vary significantly. Across the tidally-driven spawning cycle, cyp19a1b abundances were higher in females than TP males. Interestingly, cyp19a1b levels were higher in TP males close (~1 h) to the daily spawning period when sexual and aggressive behaviors rise than males far from spawning (~10-12 h). Together with earlier findings, our results suggest alterations in neural estrogen signaling are key regulators of socially-controlled sex change and sexual phenotype differences. Additionally, these patterns suggest TP male-typical sociosexual behaviors may depend on intermediate rather than low estrogenic signaling. We discuss these results and the possibility that an inverted-U shaped relationship between neural estrogen and male-typical behaviors is more common than presently appreciated.

Problems and Progress regarding Sex Bias and Omission in Neuroscience Research.

Neuroscience research has historically ignored female animals. This neglect comes in two general forms. The first is sex bias, defined as favoring one sex over another; in this case, male over female. The second is sex omission, which is the lack of reporting sex. The recognition of this phenomenon has generated fierce debate across the sciences. Here we test whether sex bias and omission are still present in the neuroscience literature, whether studies employing both males and females neglect sex as an experimental variable, and whether sex bias and omission differs between animal models and journals. To accomplish this, we analyzed the largest-ever number of neuroscience articles for sex bias and omission: 6636 articles using mice or rats in 6 journals published from 2010 to 2014. Sex omission is declining, as increasing numbers of articles report sex. Sex bias remains present, as increasing numbers of articles report the sole use of males. Articles using both males and females are also increasing, but few report assessing sex as an experimental variable. Sex bias and omission varies substantially by animal model and journal. These findings are essential for understanding the complex status of sex bias and omission in neuroscience research and may inform effective decisions regarding policy action.