Stress signaling via glucocorticoid receptor disrupts ovarian development in Japanese eel (Anguilla japonica) through HPI-HPG axis crosstalk

Gonadal development is closely linked to cortisol levels, a major stress response indicator, which is mediated by the glucocorticoid receptor (GR) in teleost fish. Stress activates the HPI axis (hypothalamic-pituitary-adrenocortical axis), triggering cortisol release, which subsequently affects the reproductive system. Therefore, GR is considered a mediator in elucidating the relationship between stress and gonadal development. In this study, we cloned and analyzed the gr1 and gr2 genes of the Japanese eel ( Anguilla japonica ). The phylogenetic tree of GR revealed that gr1 and gr2 exhibit a unique evolutionary distribution in teleost fish. Quantitative real-time PCR results indicated that gr1 and gr2 were primarily expressed in the ovary and brain. To investigate whether glucocorticoids mediate their inhibitory effects through GR, we performed in vivo DXMS injection experiments. The results indicated that DXMS stimulation significantly altered the expression of key genes in the HPG axis (hypothalamic-pituitary–gonadal axis) of the Japanese eel, particularly those related to ovarian development. Additionally, in vitro experiments with isolated brain, pituitary, and gonadal cells revealed that DXMS treatment significantly suppressed the expression of several reproduction-related genes, and the GR antagonist RU486 partially reversed this suppression. This study reveals the mechanisms through which glucocorticoids regulate ovarian development in the Japanese eel via GR and HPI-HPG axis interactions. These findings offer new insights into the role of stress in fish reproduction and provide a theoretical basis for optimizing artificial reproduction techniques in the Japanese eel.