Physiological and transcriptomic changes in zebrafish after long-term exposure from embryo to adult to environmentally relevant concentrations of norgestrel.

The potential adverse effects of progestins on aquatic organisms have increasingly raised global concern. This study conducted a full life-cycle experiment, exposing zebrafish to 28 ng/L norgestrel (NGT) from embryo to adulthood over 140 days, with a primary focus on investigating physiological and transcriptomic changes. The results indicated that long-term exposure to NGT significantly promoted the growth of zebrafish and induced a male-biased sex ratio. In males, it increased levels of FSH, 11-KT, and E2 hormones. Regarding antioxidant capacity, NGT decreased T-AOC, SOD, and POD activities and MDA levels in the brain, while increasing SOD and POD activities in the liver. This disrupted oxidative stress homeostasis, potentially contributing to hormonal imbalance and altered reproductive energy allocation. Transcriptomic analysis found significant enrichment of the estrogen signaling pathway in the brain and the steroid biosynthesis pathway in the liver and testis. In the brain, the estrogen signaling pathway demonstrated significant up-regulation of adcy3b, plcb2, krt17, krt97 and krt91 genes. In the liver, the steroid biosynthesis pathway showed an increased expression of dhcr24, sc5d, msmo1, and lss genes. In the testis, the cyp24a1 and cel.1 genes in the steroid biosynthesis pathway were also up-regulated. These gene expression changes likely drive the rise in reproductive hormones and ultimately affect reproductive function. This research underscores the substantial long-term impacts of low-dose NGT, indicating that short-term assessments might underestimate the ecological risks associated with prolonged pollutant exposure. The findings offer a crucial scientific foundation for assessing the hazards of progestin-like endocrine disruptors to aquatic organisms.