To study the epigenetic events between the interaction of the immune-reproduction system, two approaches were performed by immune-stimulating the animal model zebrafish (Danio rerio) with lipopolysaccharide (LPS)

In fish, epigenetic modifications play a key role in regulating development, growth, and adaptation to environmental factors. Interestingly, emerging evidence suggests that epigenetic mechanisms may also play a crucial role in modulating the response of the fish gonads to infectious agents. Gonadal factors, including reproductive hormones and cytokines, can modulate immune cell activities, regulate the production of immune molecules, influence the overall immune response, and have a role during gonadal sex differentiation. Although the existence of the reproductive-immune system interaction is well-known, the underlying epigenetic mechanisms require further elucidation, not only in fish but in mammals. To study the epigenetic events between the interaction of the immune-reproduction system, two approaches were performed by immune-stimulating the animal model zebrafish (Danio rerio) with lipopolysaccharide (LPS) with the following aims: 1) to study the resulting sex ratio after immune stimulating fish during gonadal development (17–30 dpf); 2) to decipher methylation patterns in two key innate immune genes caspase 9 (Casp9) and interleukin 1g?›½ (Il1g?›½) in immune-stimulated adult fish. For the study, larvae were bathed for the first approach while adults were intraperitoneally injected for the second. The DNA methylation of the two relevant innate immune genes was studied by a candidate gene approach at a single-nucleotide resolution by sequencing strategies. Results showed that sex ratios were not altered, although a feminization trend was observed after immune-stimulating fish during gonadal development. DNA methylation difference of the Casp9 gene was significant for the interaction of treatment and sex. In particular, 8 CpG islands in treated females were identified as significant, while 3 CpGs in treated males. The Il1g?›½ gene presented a sexual dimorphic difference, but not due to immunostimulant treatment. Overall data suggested the existence of an interplay between sex and immune response in the fish gonads at the epigenetic level. Data shown here helps in the understanding of these interactions, crucial venues for unraveling epigenetic mechanisms underlying sexual dimorphic immune responses in reproductive tissues.