Bisphenol AF (BPAF) jeopardizes male fertility and triggers intergenerational defects in zebrafish (Danio rerio)

Autor(es)

da Costa, Daniel Fernandes ; Borali, Luciana Marino ; Zanardini, Maya ; Sanches, Eduardo Antonio ; de Souza, Ana Regina Seabra ; Rodrigues, Maira da Silva ; de Moraes, Adriana Carvalho Natal ; Habibi, Hamid R. ; Nobrega, Rafael Henrique

• Tipo de documento: Artigo Científico
• Fonte: COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY; v. 297, p. 15-pg., 2025-07-10.

Resumo

The plasticizer Bisphenol AF (BPAF) is an emerging contaminant used in industrial production due to its high thermal and chemical stability. However, it poses a threat to public health and ecosystems. BPAF is an endocrinedisrupting xenoestrogen that can interfere with the hypothalamic-pituitary-gonadal axis and dysregulate steroid synthesis. In this study, adult male zebrafish were exposed to an environmentally relevant concentration of BPAF (0.15 mu g/L) for 14 days. The effects on 11-Ketotestosterone (11-KT) synthesis, spermatogenesis, and sperm quality were assessed. Additionally, we investigated potential impacts of BPAF on paternal information by breeding with untreated females, evaluating intergenerational effects such as delayed hatching rates, malformations, decreased survival, and gene expression changes in the offspring (F1). Furthermore, the same parameters were examined in embryos directly exposed to 0.15 mu g/L BPAF. BPAF stimulated the differentiation of both meiotic (spermatocytes) and post-meiotic (spermatids) cysts alongside with up-regulation of the meiotic prophase marker gene expression (sycp3l).. However, the differentiation observed in spermatogenesis did not appear to be mediated by 11-KT as its plasma or testicular concentrations did not show significant differences.. BPAF exposure stimulated a range of genes involved in epigenetic regulation (tet1, ezh2, kdm6b, kat6a, and hdac4) in the testes and significantly reduced sperm motility. In the F1 offspring, there was evidence of paternal information modification, including substantial delays in hatching rates, increased mortality, and elevated mRNA levels of the genes vegfa and cyp19a1b after 96 h post-fertilization (hpf). Similarly, embryos/larvae directly exposed to BPAF showed delayed hatching rates (at 72 h), increased mortality, and significant changes in gene expression, disrupting genes related to development (mstn1, vegfa, and wnt8), estrogen (esr1, cyp19a1b, and vgt1), and androgen (hsd11 beta 2). This study highlights the need to understand the effects of BPAF and its potential impacts on ecosystems, questioning its viability as an alternative to BPA. (AU)

• Processo FAPESP: 19/22997-3 - Hormônios tireoidianos e sua relação com o eixo reprodutivo-somatotrópico e seu possível papel no desenvolvimento embrionário em resposta ao estresse materno em Zebrafish (Danio rerio)
• Beneficiário: Maira da Silva Rodrigues
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 21/13146-0 - Avaliação de risco do análogo do Bisfenol A (BPAF) na espermatogênese e desenvolvimento embrionário do zebrafish
• Beneficiário: Luciana Marino Borali
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 23/01319-2 - Avaliação do impacto de florações de cianobactérias e poluentes presentes no ambiente aquático in vivo e in vitro em peixes teleósteos e sua aplicação em organóides testiculares humanos
• Beneficiário: Rafael Henrique Nóbrega
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 21/06742-5 - Novos insights sobre sinais gonadais (fatores de crescimento e lncRNAs) que regulam a maturação gonadal em peixes: conhecimento básico e desenvolvimento de estratégias biotecnológicas para retardar a puberdade
• Beneficiário: Rafael Henrique Nóbrega
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2