Induction of Masculinization in Mosquitofish by synthetic progestin etonogestrel exposure: Insights from morphological, ovary histological, and ovary transcriptomic analyses (PRJCA036358)
The demand for synthetic progesterone has surged due to its widespread use in contraceptives and veterinary drugs. However, these compounds are not fully removed by wastewater treatment plants, leading to their release into aquatic environments and potential disruption of fish reproduction and development. Etonogestrel (ETO), a third-generation synthetic progestogen, is widely used in oral contraceptives. In this study, adult female mosquitofish were exposed to ETO at concentrations of 0, 5, 50, and 500 ng/L for 36 days. Morphological, ovary histological, and ovary transcriptomic analyses were conducted to assess the effects of ETO. Results showed that ETO exposure reduced the body weight/total length ratio and promoted gonopodia and skeletal modifications, with particularly notable findings of decreased ovarian weight and induced testicular structures in the 500 ng/L group, indicating a significant masculinization effect. Transcriptomic analysis revealed that genes related to sexual differentiation (cyp17a1 and hsd17b3), which were enriched in the GnRH signaling pathway and steroid hormone biosynthesis, may drive masculinization by promoting androgen production and inhibiting estrogen synthesis. Meanwhile, upregulation of sox9 and tgfb3 may inhibit ovarian development and promote spermatogenesis. Additionally, ETO possibly promoting morphological masculinization by altering lipid metabolism pattern. These findings indicate that ETO can induce masculinization and negatively impact reproductive health in mosquitofish, potentially exacerbated by lipid metabolism changes.