Estrogen exposure overrides the masculinizing effect of elevated temperature by a downregulation of the key genes implicated in sexual differentiation in a fish with mixed genetic and environmental sex determination

Abstract

BackgroundUnderstanding the consequences of thermal and chemical variations in aquatic habitats is of importance in a scenario of global change. In ecology, the sex ratio is a major population demographic parameter. So far, research that measured environmental perturbations on fish sex ratios has usually involved a few model species with a strong genetic basis of sex determination, and focused on the study of juvenile or adult gonads. However, the underlying mechanisms at the time of gender commitment are poorly understood. In an effort to elucidate the mechanisms driving sex differentiation, here we used the European sea bass, a fish species where genetics and environment (temperature) contribute equally to sex determination.ResultsHere, we analyzed the transcriptome of developing gonads experiencing either testis or ovarian differentiation as a result of thermal and/or exogenous estrogen influences. These external insults elicited different responses. Thus, while elevated temperature masculinized genetic females, estrogen exposure was able to override thermal effects and resulted in an all-female population. A total of 383 genes were differentially expressed, with an overall downregulation in the expression of genes involved in both in testicular and ovarian differentiation when fish were exposed to Estradiol-17ß through a shutdown of the first steps of steroidogenesis. However, once the female phenotype was imposed, gonads could continue their normal development, even taking into account that some of the resulting females were fish that otherwise would have developed as males.ConclusionsThe data on the underlying mechanisms operating at the molecular level presented here contribute to a better understanding of the sex ratio response of fish species subjected to a combination of two of the most common environmental perturbations and can have implications in future conservational policies.

Transcriptome of Gonads From High Temperature Induced Sex Reversal During Sex Determination and Differentiation in Chinese Tongue Sole, Cynoglossus semilaevis

“…For example, Nile tilapia ( Oreochromis niloticus ) exposed to elevated temperature can override genetic sex determination, and the females can be reversed to produce pseudomales (Baroiller et al, 2009). Blue tilapia ( Oreochromis aureus ), Japanese flounder ( Paralichthys olivaceus ), European sea bass ( Dicentrarchus labrax ), turbot ( Scophthalmus maximus ) and Atlantic silverside ( Menidia menidia ) also undergo temperature induced ESR (Conover and Fleisher, 1986; Desprez and Mélard, 1998; Yamaguchi et al, 2007; Diaz and Piferrer, 2015; Robledo et al, 2015; Diaz and Piferrer, 2017).…”

Sex Determination and Differentiation in Teleost: Roles of Genetics, Environment, and Brain

“…A recent study in the European sea bass showed that genes related to ovarian differentiation such as wisp1, cyp19a, and 17β-hsd and testicular differentiation such as amh, dmrt1, and tesc are downregulated after exposure to high temperature and E2 treatment. Suppression of all these genes results in the feminisation of the fish [158]. However, a contrasting report showed an increase in cyp19a gene expression following E2 treatment and suppression of cyp19a following exposure to high-temperature results in masculinisation [159].…”

“…A wide range of natural E2, synthetic oestrogen, and synthetic androgen (17α-methyltestosterone) have been used to produce monosex fish. Both types of steroids are readily metabolized post-treatment [152,158,159].…”

Expression and characterization of the cyp19a gene and its responses to estradiol/letrozole exposure in Chinese soft‐shelled turtle (Pelodiscus sinensis)

“…Aromatase catalyzes the conversion of androgens into estrogens, a process that is essential to sex differentiation and sex development. As a critical gene in estrogen biosynthesis, cyp19a influences gonadal differentiation processes and the population sex ratio by regulating the biosynthesis of gonadal steroid hormones in birds (Smith & Sinclair, ; Vaillant, Dorizzi, Pieau, & Richard‐Mercier, ), teleost fish (Caruso, Breton, & Berlinsky, ; Díaz & Piferrer, ), amphibians (Nakamura, ; Olmstead et al, ), and reptiles (Jeyasuria & Place, , Ramsey & Crews, ). The use of specific aromatase agonists or aromatase inhibitors can cause genetic males to display female phenotypes, and genetic females to display male phenotypes, in various vertebrate species.…”

“…Analysis of the expression of cyp19a and estrogen production in the American alligator showed that cyp19a is not the initial trigger for alligator sex determination, but played a necessary role in ovarian differentiation (Gabriel, Blumberg, Sutton, Place, & Lance, ). Exposure of fish to exogenous estrogens during sexual differentiation had a profound effect on reprogramming their gonadal transcriptome, resulting not only complete feminization of the population but in inhibition of steroidogenesis in developing females (Díaz & Piferrer, ).…”