Sex Differences in Aromatase Gene Expression in the Medaka Brain

Abstract

The brain of teleost fish exhibits a significant degree of sexual plasticity, even in adulthood. This unique feature is almost certainly attributable to a teleost-specific sexual differentiation process of the brain, which remains largely unknown. To dissect the molecular basis of sexual differentiation of the teleost brain, we searched for genes differentially expressed between both sexes in the medaka brain. One gene identified in the screen, cyp19a1b, which encodes the steroidogenic enzyme aromatase, was selected for further analysis. As opposed to the situation in most vertebrates, medaka cyp19a1b is expressed at higher levels in the adult female brain than the male brain. The female-biased expression in the brain is consistent regardless of reproductive or diurnal cycle. Medaka cyp19a1b is expressed throughout the ventricular zones in wide areas of the brain, where, in most regions, females have a greater degree of expression compared to males, with the optic tectum exhibiting the most conspicuous predominance in females. Contrary to what is known in mammals, cyp19a1b expression exhibits neither a transient elevation nor a sex difference in medaka embryos. It is not until just before the onset of puberty that cyp19a1b expression in the medaka brain is sexually differentiated. Finally, cyp19a1b expression in the medaka brain is not under the direct control of sex chromosome genes but relies mostly, if not solely, on oestrogen derived from the gonad. These unique properties of aromatase expression in the brain probably contribute substantially to the less rigid sexual differentiation process, thus ensuring remarkable sexual plasticity in the teleost brain.

Steroid modulation of neurogenesis: Focus on radial glial cells in zebrafish

“…Data recently obtained in our laboratory demonstrated that in amphibian, aromatase expression is restricted to neurons during development as in adulthood [81]. In adult zebrafish, we did not observe sexual dimorphism in the expression of AroB (transcripts and protein) while in medaka, females exhibit a stronger periventricular expression in several regions, in particular the optic tectum [73].…”

“…The small number of labeled cells and the fact that this antibody was raised against human aromatase now suggest that these results were artifactual. Since Forlano et al work until the most recent publications in fish [71], the development of homologous and specific molecular tools such as cyp19a1b riboprobes and AroB antibodies has revealed in many teleost species a high number of AroB-expressing cells in ventricular position in the forebrain and midbrain, consistent with the strong aromatase enzymatic activity [64,68,[71][72][73]. In zebrafish, cyp19a1b messengers are strongly expressed along the ventricles in the olfactory bulbs, telencephalon, preoptic area, hypothalamus, thalamus and optic tectum [74].…”

“Brain sex differentiation” in teleosts: Emerging concepts with potential biomarkers

“…We presume that the sexual dimorphism of cyp19a1b certainly influence brain sex differentiation because of its ability to 'estrogenize' the brain (Table 1). Interestingly, in the Japanese medaka, it is not until before the onset of puberty that cyp19a1b expression is sexually differentiated (Okubo et al, 2011; Table 1). It is also documented that cyp19a1b is a target for xenoestrogens in the same species (Kuhl et al, 2005; Table 1).…”

“…cyp19a1b, GTHs Kuhl et al (2005) cyp19a1b triggers abnormal sex differentiation in xenoestrogens treated fish Patil and Gunasekera (2008) cyp19a1b contributes for neural development and possibly sexual behavior and found at high levels in adult female brain Okubo et al (2011) Female biased expression of cyp19a1b Weltzien et al (2013) Slow/late origin of gonadotrope cells and GTHs 13…”

Female-specific target sites for both oestrogen and androgen in the teleost brain

“…The sections were digested with proteinase K (Wako Pure Chemical Industries, Osaka, Japan) for 15 min at 378C, postfixed with 4 per cent PFA for 10 min, and acetylated with 0. 25 (d) Examination of genetic and phenotypic sex dependence of ER and AR expression Sex-inverted medaka were produced as described previously [14]. Briefly, fertilized eggs were incubated at high temperature (328C) and simultaneously received 0.2 ng ml 21 methyltestosterone until hatching, which led to the production of XX males.…”