Timeline of sex differentiation and stabilization in zebrafish: Interplay between methyl-sensitive transcription factors, prostaglandin-related genes and DNA methylation.

The processes by which an individual develops as a male (testis) or female (ovary) are remarkably diverse across taxa. While sex is determined by genetic factors in some species, it can be determined by environmental factors in others. Despite these discrepancies, common features are however observed. For species as distant as drosophila and humans, the ovary or testis arises from a bipotential gonad. Thus, each embryo has the potential to develop as a male or female. Given the growing evidence that global change can affect the sexual fate and fertility of individuals across taxa, there is a critical need to understand the mechanisms involved in sex differentiation and maintenance. In the present work, we followed the transcription and methylation levels of genes known, or suspected, to be involved in sex differentiation throughout zebrafish development. Early sex differentiation was marked by sex-specific transcription patterns of genes encoding for methyl-sensitive transcription factors of the zbtb family and for sox9a and zar1, establishing common features with mammals. In contrast, our results suggest that sex markers such as cyp19a1a, dmrt1, foxl2a or amh are mainly involved in sex stabilization and maintenance. DNA methylation appeared to be at the interface, playing a role in sex differentiation and maintenance by progressively constraining plasticity and stabilizing the transcription of genes under study. Our results also highlighted significant changes in the transcription level of genes involved in prostaglandins production during the ovary-to-testis transition, suggesting a potential role of these mediators in DNA methylation reprogramming and sex differentiation.