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双酚 F(双酚 A 的一种类似物)对雄性大鼠生殖功能的影响。

Effect of bisphenol F, an analog of bisphenol A, on the reproductive functions of male rats.

机构信息

Reproductive Physiology Lab, Department of Animal Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.

出版信息

Environ Health Prev Med. 2019 Jun 10;24(1):41. doi: 10.1186/s12199-019-0797-5.

Abstract

OBJECTIVE

Bisphenol A (BPA) is a monomer primarily used in the production of polycarbonate plastic and epoxy resins. Bisphenol F (BPF) is apparently the main BPA replacement that is used increasingly. BPF has been detected in canned food, thermal paper receipts, and soft drinks. In the present experiment, we did both in vitro and in vivo studies to evaluate the effect of low and high-dose BPF exposures on testosterone concentration, oxidative stress, and antioxidants activity in reproductive tissues of male rats.

METHODS

Adult (80-90 days old) male Sprague Dawley rats (n = 36) obtained from the rodent colony of Animal Sciences Department of Quaid-i-Azam University. The direct effects of BPF on the antioxidant enzymes and testosterone secretion were measured in vitro and in vivo studies. In an in vivo experiment, adult male Sprague Dawley rats (n = 42) were exposed to different concentrations of bisphenol F (1, 5, 25, and 50 mg/kg/d) for 28 days. Various biochemical parameters were analyzed including the level of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), reactive oxygen species (ROS), and lipid peroxidation (LPO). Moreover, sperm motility, daily sperm production (DSP), comet assay, and histological analysis were performed.

RESULTS

In vitro study showed that BPF exposure significantly (p < 0.05) induced oxidative stress biomarkers, i.e., ROS and LPO, while it did not change antioxidant enzyme and testicular testosterone concentration. Whereas, an in vivo study revealed that BPF induced dose-dependent effect and high-dose (100 mg/kg) exposure of BPF significantly reduced tissue protein (p < 0.05) content, CAT (p < 0.001), SOD (p < 0.05), and POD (p < 0.05) levels while significantly (p < 0.05) augmented ROS and lipid peroxidation. Furthermore, BPF reduces testosterone, LH, and FSH secretion in a dose-dependent manner. Significant (p < 0.001) reduction in plasma and intra-testicular testosterone, LH, and FSH was noticed at 100 mg/kg BFP dose. High-dose exposure reduces spermatogenesis.

CONCLUSION

BPF showed an antagonistic effect on male reproductive hormones and induce alterations in testicular morphology. Increased oxidative stress and decreased testicular antioxidant status might be the underlying mechanism of BFP-induced testicular toxicity.

摘要

目的

双酚 A(BPA)是一种主要用于生产聚碳酸酯塑料和环氧树脂的单体。双酚 F(BPF)显然是 BPA 的主要替代品,其使用量正在逐渐增加。BPF 已在罐头食品、热敏纸收据和软饮料中被检测到。在本实验中,我们进行了体外和体内研究,以评估低剂量和高剂量 BPF 暴露对雄性大鼠生殖组织中睾酮浓度、氧化应激和抗氧化剂活性的影响。

方法

成年(80-90 天龄)雄性 Sprague Dawley 大鼠(n=36)来自于 Quaid-i-Azam 大学动物科学系的啮齿动物群体。在体外和体内研究中测量了 BPF 对抗氧化酶和睾酮分泌的直接影响。在体内实验中,成年雄性 Sprague Dawley 大鼠(n=42)暴露于不同浓度的双酚 F(1、5、25 和 50mg/kg/d)28 天。分析了各种生化参数,包括过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、过氧化物酶(POD)、活性氧(ROS)和脂质过氧化(LPO)的水平。此外,还进行了精子活力、每日精子产量(DSP)、彗星试验和组织学分析。

结果

体外研究表明,BPF 暴露显著(p<0.05)诱导了氧化应激生物标志物,即 ROS 和 LPO,而不改变抗氧化酶和睾丸睾酮浓度。然而,体内研究表明,BPF 诱导了剂量依赖性效应,高剂量(100mg/kg)BPF 暴露显著降低了组织蛋白(p<0.05)含量、CAT(p<0.001)、SOD(p<0.05)和 POD(p<0.05)水平,同时显著增加了 ROS 和脂质过氧化。此外,BPF 以剂量依赖性方式降低了睾酮、LH 和 FSH 的分泌。在 100mg/kg BFP 剂量下,血浆和睾丸内睾酮、LH 和 FSH 的显著(p<0.001)降低。高剂量暴露降低了精子发生。

结论

BPF 对雄性生殖激素表现出拮抗作用,并引起睾丸形态的改变。氧化应激增加和睾丸抗氧化状态降低可能是 BPF 诱导睾丸毒性的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a89/6558835/c7702215e837/12199_2019_797_Fig1_HTML.jpg

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