Odetayo Adeyemi Fatai, Adeyemi Wale Johnson, Olayaki Luqman Aribidesi
Physiology Department, University of Ilorin, Ilorin, Nigeria.
Physiology Department, Federal University of Health Sciences, Ila Orangun, Nigeria.
Front Reprod Health. 2023 Aug 2;5:1204728. doi: 10.3389/frph.2023.1204728. eCollection 2023.
Bisphenol F (BPF), an alternative to bisphenol A has been implicated as a gonadotoxic substance. BPF has been shown to induce hormonal imbalance and testicular oxidative damage. However, the mechanism associated with BPF-induced testicular toxicity has not been fully explored. This study was designed to explore the role of tumor protein (p53)/ B-cell lymphoma 2 (BCl-2) signaling and oestrogen receptor beta (Erβ) in BPF-induced testicular toxicity.
Male Wistar rats were randomized into control (Cntrl), BPF-treated (10, 30, and 50 mg/kg for low dose (BPF-L), medium dose (BPF-M), and high dose (BPF-H) respectively), and BPF-treated recovery (Cntrl-R, BPF-L-R, BPF-M-R, and BPF-H-R). The administration was via gavage and lasted for 28 days and the animals in the recovery groups were allowed 28-days exposure free period for recovery from BPF exposure.
BPF resulted in the distortion of the testicular histoarchitecture, which was accompanied by a significant rise in testicular gamma-lutamyl transferase and lactate dehydrogenase activities but a decline in sorbitol dehydrogenase activities. Also, BPF caused a significant reduction in plasma gonadotropin-releasing hormone, luteinising hormone, follicle-stimulating hormone, and testosterone, which was associated with the downregulation of testicular 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase activities. Furthermore, BPF induced testicular inflammation, redox imbalance, and apoptosis, accompanied by distortion in p53/BCl-2 signaling and overexpression of Erβ. Again, the observed toxic effects of BPF were dose-dependent and not completely reversed by BPF cessation.
Bisphenol F induced gonadotoxicity by distorting p53/BCl2 signaling and the expression of Erβ. These observed alterations were not completely reversed after the cessation of BPF exposure.
双酚F（BPF）作为双酚A的替代品，被认为是一种性腺毒性物质。已表明BPF会导致激素失衡和睾丸氧化损伤。然而，与BPF诱导的睾丸毒性相关的机制尚未得到充分探索。本研究旨在探究肿瘤蛋白（p53）/B细胞淋巴瘤2（Bcl-2）信号通路和雌激素受体β（Erβ）在BPF诱导的睾丸毒性中的作用。
将雄性Wistar大鼠随机分为对照组（Cntrl）、BPF处理组（低剂量（BPF-L）、中剂量（BPF-M）和高剂量（BPF-H）分别为10、30和50mg/kg）以及BPF处理后恢复组（Cntrl-R、BPF-L-R、BPF-M-R和BPF-H-R）。通过灌胃给药，持续28天，恢复组动物在停止BPF暴露后有28天的恢复期。
BPF导致睾丸组织结构变形，并伴有睾丸γ-谷氨酰转移酶和乳酸脱氢酶活性显著升高，但山梨醇脱氢酶活性下降。此外，BPF导致血浆促性腺激素释放激素、黄体生成素、卵泡刺激素和睾酮显著降低，这与睾丸3β-羟基类固醇脱氢酶和17β-羟基类固醇脱氢酶活性下调有关。此外，BPF诱导睾丸炎症、氧化还原失衡和细胞凋亡，同时伴有p53/Bcl-2信号通路紊乱和Erβ过表达。再者，观察到的BPF毒性作用呈剂量依赖性，停止BPF给药后并未完全逆转。
双酚F通过扭曲p53/Bcl2信号通路和Erβ的表达诱导性腺毒性。停止BPF暴露后，这些观察到的改变并未完全逆转。
