Transgenerational epigenetic sex determination: Environment experienced by female fish affects offspring sex ratio

Epigenetic Transgenerational Modifications Induced by Xenobiotic Exposure in Zebrafish

“…Long-term evaluation studies (at least up to F3) are necessary to assess the persistence of epigenetic marks; in this regard, the information available is scarce (only 3 publications reach F3), and the results are inconsistent, which could be related to the epigenetic mark under study and the analytical method. For instance, there are studies in which epigenetic marks (such as DNA methylation) persist until F3 (Kamstra et al, 2018), while in other studies the same epigenetic marks decrease (Pierron et al, 2021) or are not observed even in F2 (Santangeli et al, 2019). This indicates that studies must analyze in detail the possible epigenetic marks, as well as the methodological limitations.…”

“…When a transgenerational effect occurs, the epigenetic mark is mitotically and meiotically stable without reprogramming itself in primordial germ cells and postfertilization embryos. The levels of 5-methylcytosine (5-mC) can be measured in a simplified "one-step" ELISA type reaction; however this footprint may be biased since not all xenobiotics produce the same effect on methylation levels, and each cell type may express a different signature throughout development and different life stages (Santangeli et al, 2019;Pierron et al, 2021). For instance, no differences were observed in F0 and subsequent generations after bisphenol-A (BPA) and arsenic (As) exposure (Santangeli et al, 2019;Valles et al, 2020), while different levels of DNA methylation were observed in different generations after exposure to chlorpyrifos (F1 and F2 showed hypomethylation, whereas F3 presented hypermethylation) probably due to a paternal and/or maternal influence (Schmitt et al, 2020).…”

“…For example, it has been reported that BPA exposure generates locus-specific DNA methylation changes associated with reproductive disturbances in males and females (dnmt1, anti-müllerian hormone (amh), folliclestimulating hormone receptor (fshr), Sry-box transcription factor 2 (sox2), and insulin receptor b (insrb) (Lombó et al, 2015;Santangeli et al, 2019). Also, cadmium (Cd) exposure showed changes in the promoter of the forkhead boxl2a (foxl2a) gene (which is involved in ovary maintenance; Yang et al, 2017) in female gonads from F0 to F3, resulting in the progressive feminization of the population over generations (Pierron et al, 2021). In permethrin exposure, changes of DMR in both sexes on chromatin remodeling 24 (chr24) and vimentin (vim) genes were observed, with modifications in the same sites from F0 to F2; furthermore, sex-specific differentially methylated regions (DMR) were found related to the paternal inheritance of F0 to F2 in fragile-X mental retardation protein translational regulator 1 (fmr1) and prepronociceptin b (pnocb) genes, both related to the development of the zebrafish nervous system (Blanc et al, 2021).…”

Multigenerational exposure to gamma radiation affects offspring differently over generations in zebrafish

“…Selection of couples based on secondary sexual characteristics had been proven to be difficult, and when sex was determined after dissection of adults, the sex ratio was significantly biased in favor of males, with 4 and 1.8 times lower numbers of females for F1-I5 and for F1-R5, respectively. Irradiation could affect sex differentiation as previously observed after exposure to hypoxia, high temperature and pollutants in zebrafish (Brion et al, 2004;Pierron et al, 2021;Valdivieso et al, 2020;Wang et al, 2011). Exposure to heat in fish is usually known to increase the number of males.…”

“…We used domesticated zebrafish (Danio rerio AB strain), which develop rapidly, have high fecundity, and are well described in the literature (Lawrence, 2007). Danio rerio is often used in ecotoxicology, for the assessment of stress effects in general and more recently for the characterization of multi-or transgenerational effects of stressors (Baker et al, 2014;Lin et al, 2020;Pierron et al, 2021;Siegenthaler et al, 2017;Simon et al, 2014). Moreover, zebrafish have been already used in studies assessing the effects of ionizing radiation (Epperly et al, 2012;Gagnaire et al, 2015;Houdigui et al, 2020;Hurem et al, 2017a;Hurem et al, 2018;Kamstra et al, 2018;Kong et al, 2016;Simon et al, 2011a).…”