Acute exposure to antimony elicits endocrine disturbances, leading to PCOS and ovarian fibrosis in female zebrafish

Abstract

Antimony (Sb) is an estrogenic metal. Exogenous exposure to Sb can affect estrogen levels and their receptor expression in organisms, exerting estrogen-disrupting effects and even inducing polycystic ovary syndrome (PCOS), which is accompanied by the progression of ovarian fibrosis. To investigate the pathological mechanism of this reproductive damage caused by Sb exposure, we exposed female zebrafish to Sb solution for 18 days for acute toxicity experiments. The results showed that Sb exposure affected the changes of GnRH, FSH, LH, E2 and T levels on the HPG axis, which disrupted the balance of sex steroid hormones in the internal environment of zebrafish and progression of PCOS. Furthermore, Sirius red staining revealed significant fibrosis in the ovarian tissues of Sb-exposed female zebrafish. This study adopted transcriptome sequencing and Western Blotting to explore the mechanisms of action. The biological processes and signaling pathways potentially associated with Sb-induced ovarian fibrosis were predicted by using GO annotation and KEGG pathway enrichment analysis, such as ECM receptors, TGF-β/Smad and WNT/β-catenin. The experiment results showed that Sb induced up-regulation of the transcription levels of the pro-fibrotic factors tgf-β3, wnt10a, ctnnb1, and β-catenin protein expression, suggesting the activation of the WNT/β-catenin pathways and TGF-β/Smad. Sb exposure led to up-regulation of ECM-related genes col2a1a, itgb1b.2, lamc1, fn1a and up-regulation of fibrosis markers α-SMA, Fn1a, col4a2 protein expression, Therefore, we hypothesized that Sb exposure activates the TGF-β/Smad and WNT/β-catenin pathways, leading to abnormal ECM deposition and promoting the progression of ovarian fibrosis in zebrafish.