The expression of liver–gonadal axis genes reveals the long–term effects of exogenous estradiol on gonad development and liver function in GIFT tilapia

The aim of this study was to investigate the effects of exogenous estradiol on the expression of the liver–gonadal axis gene in GIFT tilapia. Larval fish (5 dph) were fed a diet with 100 mg kg⁻¹ 17α–ethynylestradiol (EE2) for 30 days and then transferred to a conventional diet. Sex reversal statistics revealed that more than 60 % of the genotypic male fish transformed into pseudofemales. Histological results showed that the oocytes in pseudofemales developed asynchronously and had a prolonged maturation time compared to those in normal female fish. Global expression and DNA methylation analyses revealed that the expression patterns of the gonad and liver genes in pseudofemales were similar to those in XX female fish. Compared to XY male fish, the differentially expressed genes (DEGs) in pseudofemale gonads were enriched in FoxO signaling pathway, oocyte meiosis and other hormone–regulated pathways, which may affect the growth and development of the ovary. Moreover, the DEGs in liver were enriched mainly in protein digestion and absorption, steroid biosynthesis, and some disease and energy metabolism pathways, which may affect liver immunity and energy metabolism. Furthermore, the co-upregulated genes in the liver and gonads were enriched mainly in steroid biosynthesis and glycolysis/gluconeogenesis, whereas the co-downregulated genes were enriched in GnRH secretion and oxytocin signaling pathway. In addition, some genes associated with hormone secretion, growth, metabolism, and immunity in the liver‒gonad axis, such as Oxt, Spoll and Piwi12, were activated, whereas Hox, cyp21a, gas1 and other genes were inhibited. These results indicated that EE2 affects gene expressions in liver and gonad tissues through the hypothalamic–pituitary–gonadal–liver (HPGL) axis.