Costa Daniel Fernandes da, Borali Luciana Marino, Zanardini Maya, Sanches Eduardo Antonio, de Souza Ana Regina Seabra, da Silva Rodrigues Maira, de Moraes Adriana Carvalho Natal, Habibi Hamid R, Nóbrega Rafael Henrique
Reproductive and Molecular Biology Group, Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), 18618-970 Botucatu, São Paulo, Brazil.
Department of Biological Sciences, University of Calgary, Calgary, AB 2500, Canada.
Comp Biochem Physiol C Toxicol Pharmacol. 2025 Jul 7;297:110278. doi: 10.1016/j.cbpc.2025.110278.
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 endocrine-disrupting 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 μg/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 μg/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 (hsd11β2). 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.
增塑剂双酚AF（BPAF）因其高热稳定性和化学稳定性而成为工业生产中一种新兴的污染物。然而，它对公众健康和生态系统构成威胁。BPAF是一种内分泌干扰性外源性雌激素，可干扰下丘脑-垂体-性腺轴并使类固醇合成失调。在本研究中，成年雄性斑马鱼暴露于环境相关浓度的BPAF（0.15μg/L）中14天。评估了其对11-酮睾酮（11-KT）合成、精子发生和精子质量的影响。此外，我们通过与未处理的雌性斑马鱼繁殖，评估后代（F1）的孵化率延迟、畸形、存活率降低和基因表达变化等代际效应，研究了BPAF对父本信息的潜在影响。此外，还对直接暴露于0.15μg/L BPAF的胚胎进行了相同参数的检测。BPAF刺激了减数分裂期（精母细胞）和减数分裂后期（精子细胞）囊肿的分化，同时上调了减数分裂前期标记基因表达（sycp3l）。然而，精子发生过程中观察到的分化似乎不是由11-KT介导的，因为其血浆或睾丸浓度没有显著差异。BPAF暴露刺激了睾丸中一系列参与表观遗传调控的基因（tet1、ezh2、kdm6b、kat6a和hdac4），并显著降低了精子活力。在F1后代中，有证据表明父本信息发生了改变，包括受精后96小时（hpf）孵化率大幅延迟、死亡率增加以及vegfa和cyp19a1b基因的mRNA水平升高。同样，直接暴露于BPAF的胚胎/幼体表现出孵化率延迟（72小时时）、死亡率增加以及基因表达的显著变化，干扰了与发育（mstn1、vegfa和wnt8）、雌激素（esr1、cyp19a1b和vgt1）和雄激素（hsd11β2）相关的基因。本研究强调了了解BPAF的影响及其对生态系统潜在影响的必要性，对其作为BPA替代品的可行性提出了质疑。
