Cadmium-induced disruption of HPG axis and methylation regulation of sex hormone synthesis in male loach Misgurnus anguillicaudatus.

Abstract

Cadmium (Cd) can affect fish reproduction by interfering with sex hormones; however, its specific effects on endocrine disruption of the hypothalamic-pituitary-gonadal (HPG) axis, DNA methylation regulation and testicular tissue in male fish remain unclear. In this study, male loaches (Misgurnus anguillicaudatus) were exposed to CdCl₂ at different concentrations. HPG axis hormones and the expression of related genes were measured after 15, 30 and 45 days of exposure. Meanwhile, the content of aromatase (cytochrome P450 19A1, CYP19A1), the key rate-limiting enzyme in sex steroid synthesis, the transcription level of its encoding gene cyp19a1a, and the DNA methylation status of its promoter region were measured, and histopathological changes in the testis were observed. The results indicated that, in the early stages of exposure (15 days), Cd induced a surge in gonadotropin-releasing hormone (GnRH) secretion, causing fluctuations in HPG axis hormones and activating CYP19A1, which led to an imbalance in the 17β-estradiol/testosterone (E2/T) ratio; this activation may have been associated with Cd-induced reduction in DNA methylation levels in the cyp19a1a promoter region and promotion of gene transcription. CpG sites in the cyp19a1a promoter region were associated with the binding site of steroidogenic factor 1 (NR5A1), suggesting that Cd regulation of DNA methylation may have involved NR5A1. Histological analysis of the testis showed that Cd exposure impaired germ cell development, and prolonged exposure to high concentrations could induce the appearance of oogonia, suggesting that Cd posed a potential risk of interfering with gonadal development in male loaches and inducing feminization.

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