Induction of Female-to-Male Sex Change in Adult Zebrafish by Aromatase Inhibitor Treatment

Abstract

This study investigated whether undifferentiated germ and/or somatic stem cells remain in the differentiated ovary of a species that does not undergo sex changes under natural conditions and retain their sexual plasticity. The effect of aromatase inhibitor (AI)-treatment on sexually mature female zebrafish was examined. A 5-month AI treatment caused retraction of the ovaries after which testes-like organs appeared, and cyst structures filled with spermatozoa-like cells were observed in sections of these tissues. Electron microscopic observations revealed that these cells appeared as large sperm heads without tails. Sperm formation was re-examined after changing the diet to an AI-free food. A large number of normal sperm were obtained after eight weeks, and no formation of ovarian tissue was observed. Artificial fertilization using sperm from the sex-changed females was successful. These results demonstrated that sex plasticity remains in the mature ovaries of this species.

Simultaneous exposure to estrogen and androgen resulted in feminization and endocrine disruption

“…In contrast, Cyp11a1, 3b-HSD, Cyp17a1 and Cyp11b2 were not observed in the testis of XY fish until 30 dah (Kobayashi et al 1996, Morrey et al 1998. In a recent study of gonadal transcriptomes from the Nile tilapia, we further confirmed that almost all steroidogenic enzyme genes, including cyp19a1a but not including cyp11b2, were up-regulated in the XX gonads at 5 dah, while these enzyme genes, including cyp11b2 but not including cyp19a1a, were detected at 30 dah and significantly up-regulated from 90 dah onwards in the XY gonads (Takatsu et al 2013). The pivotal role of estrogens in sex determination and differentiation has been demonstrated in various teleosts (Piferrer et al 1994, D'Cotta et al 2001, Kobayashi et al 2003, Vizziano et al 2008) and other non-eutherian vertebrates (Wibbels & Crews 1994, Merchant-Larios et al 1997, Hudson et al 2005.…”

“…However, this is opposite to the facts: i) it is easy to induce 100% female to male sex reversal but it is difficult to induce 100% male to female sex reversal and ii) secondary sex reversal of ovary into testis has been reported in medaka, zebrafish and tilapia (Poonlaphdecha et al 2013, Takatsu et al 2013, while there Figure 5 Expression profiles of methyltransferase genes in gonads. The expression levels of the maintenance methyltransferase gene dnmt1 were up-regulated significantly, while the expression levels of the de novo DNA methyltransferases genes dnmt3 and dnmt7 were down-regulated in the MTCE 2 -XX gonad but up-regulated in the MTCE 2 -XY gonad significantly compared with their respective control.…”

A Structurally and Functionally Common Unit in Testes and Ovaries of Medaka <b><i>(Oryzias latipes)</i></b>, a Teleost Fish

“…On the basis of this unit, structural differences and similarities of testes and ovaries can be simply understood. It has been recently discovered that mature adult ovaries can be transdifferentiated into functional testes in several teleosts, including medaka [Paul-Prasanth et al, 2013], tilapia [Sun et al, 2014], and zebrafish [Takatsu et al, 2013] by inhibiting estrogen production. Testicular tissues have been suggested to originate from the germinal epithelium of ovaries [Paul-Prasanth et al, 2013], supporting the notion that the testis is an expanded version of the germinal epithelium within which spermatogenesis occurs in an organized manner.…”

Genetic basis and biotechnological manipulation of sexual dimorphism and sex determination in fish

“…When XX medaka was exposed to high water temperature, the physiological males could be induced along with decreasing expression of cyp19a1a, whereas co-treatment with 17β-estradiol (E2) inhibited the sex reversal [116]. Besides sex hormone, aromatase inhibitors (Fadrozole and Letrozole) could reduce the enzyme activity and thereby led to masculinization, which had been used to induce female-to-male sex reversal in tilapia and medaka [117,118]. Godwin analyzed the influence of social factors on sex determination and differentiation of reef fish, and explored the advantages of this plasticity mechanism in evolution [119].…”