Oxidative stress and apoptotic pathways mediate BDE-47-induced reproductive dysfunction and offspring skeletogenesis disruption in zebrafish

Abstract

2, 2′, 4, 4′-tetrabromodiphenyl ether (BDE-47) has been recognized as a potential hazard to the reproductive systems of organisms. However, the reproductive toxicity and transgenerational effects of BDE-47 in female remain insufficiently characterized. In this study, we systematically investigated the reproductive performance, sex hormone levels, ovarian morphology, expression of genes associated with the hypothalamic-pituitary-gonadal (HPG) axis, and ovaries apoptotic responses following a 21-day exposure to BDE-47 in female zebrafish. Furthermore, we examined the intergenerational impacts of BDE-47 on unexposed F1 larvae by evaluating craniofacial skeletons and vertebrae development, oxidative stress responses, and apoptotic activity. In female zebrafish, our findings indicate that exposure to BDE-47 significantly compromised somatic indices (CF and GSI), diminished levels of steroid hormones (FSH, LH, T, and E₂), and disrupted ovarian histoarchitecture and oocyte development. These deleterious effects are likely attributable to the dysregulation of genes associated with the HPG axis and the exacerbation of apoptotic processes specifically within ovarian tissue. In F1 larvae, maternal BDE-47 exposure altered the transcriptional levels of genes involved in bone development (dlx2a, col2a1, sp7), resulting in malformations of the craniofacial skeleton and vertebrae. Additionally, BDE-47 exposure upregulated the activity of antioxidant enzyme (CAT), and modified the expression of oxidative stress-related genes (sod, cat, gpx) and apoptosis-related genes (bcl2a, baxa), indicating the activation of oxidative stress and apoptotic pathways. Collectively, our study suggest that exposure to BDE-47 not only compromises female reproductive health but also has lasting effects on offspring health, likely through mechanisms involving oxidative stress and apoptosis. The transgenerational impact, especially regarding skeletal and developmental malformations, highlights the possible hazards associated with environmental contaminants like BDE-47 on aquatic organisms and potentially, on human health.