Evidence for potential critical windows of immune development in the marine medaka (Oryzias melastigma)

The developmental origins of health and disease hypothesis suggests that environmental exposures during early immune development may trigger long-term immune pathologies. However, the timing of sensitive developmental windows in the innate immune system of vertebrates remains poorly defined. Here, we propose the marine medaka fish (Oryzias melastigma) as a model organism to define a molecular timeline for innate immune system maturation. To identify critical windows of immune development, we assessed both organismal resistance to bacterial infection and molecular markers of immune gene expression across developmental stages. Immune competence evaluation in embryos and larvae revealed distinct windows of vulnerability to bacterial challenge, suggesting dynamic immune regulation. 17α-Ethinylestradiol (EE2), a potent synthetic estrogen is known to affect both reproductive and immune function. Embryos and larvae were exposed to EE2 during three key periods (7-11 days post fertilization (dpf), 3-5 days post hatching (dph), and 12-19 dph) and subsequently challenged with a bacterial pathogen. EE2 exposure during the embryonic (7-11 dpf) and later larval (12-19 dph) periods significantly reduced pathogen resistance in a non-monotonic dose response manner, altered the expression of immune-related genes involved in protein synthesis and ribosome biogenesis and modified energy and amino acid metabolism. Altogether, this study underscores the importance of identifying sensitive periods in immune development when evaluating environmental risks and support the use of marine medaka as a relevant model for developmental immunotoxicity.