摘要:
双酚A(bisphenol A,BPA)作为典型的环境雌激素,在环境中广泛存在,具有接触机会频繁、剂量累积、潜伏期长等特点,是对生殖系统危害极大的一类污染物。研究表明BPA可在地表水、野生动物体内检测出,甚至在健康人群的体液中存在,尤其在婴儿体内含量较高。BPA进入机体后可通过I相和II相代谢酶分解,其分解产物的毒性目前仍不清楚。BPA在体内发挥雌激素样作用,与雌二醇竞争性地结合到雌激素受体上,阻碍雄激素受体的活性,促进促黄体生成素与催乳素的合成,最终抑制雄性激素的合成。BPA可破坏血睾屏障,直接刺激睾丸细胞的凋亡并导致精子质量下降,其中主要通过影响下丘脑-垂体-性腺轴(HPG)上促性腺激素释放激素受体(GnRHR)、促黄体生成素受体(LHRβ)和促卵泡雌激素(Fshb)的表达和直接刺激睾丸和附睾细胞,降低睾酮合成酶的表达及活性,抑制与精子生成相关蛋白的表达,从而影响生殖能力。同时,BPA代谢过程中消耗大量的抗氧化酶,产生氧自由基,其氧化产物可能会对睾丸和附睾的损伤形成二次打击。总之,双酚A造成雄性生殖损伤障碍主要是损伤HPG轴正负反馈调节的平衡以及影响调节激素相关基因的表达和直接损伤睾丸细胞和精子质量。
关键词:
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双酚A
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生殖毒性
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含量检测
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代谢
Abstract:
Bisphenol A (BPA) is one of the xenoestrogens and being used as agent for endocrine disruption. The impacts of BPA on male infertility have been investigated in several animal species including fish (in river and lake) as well as in humans. It is metabolized by phase I and phase II enzyme, as a substrate for the ipso-metabolism catalyzed by microsomal cytochrome P450 (CYP450). BPA interrupts the androgen receptor activity and competitively combines with estrogen receptor, thereby increasing the levels of prolactin and LH, decreasing the level of testosterone. BPA stimulates the testicular cell apoptosis and decreases the testosterone synthetase activity through the hypothalamus- pituitary- gonad (HPG) axis regulation. The relative gene expression reveals an increase in gonadotropin releasing hormone receptor (GnRHR), luteinizing hormone beta (LHRβ) and follicle stimulating hormone beta (FSHβ), Continuous exposure to BPA can lead to impairing functioning in sexual development, reproduction and behavior. BPA also decreases sperm motility and motion kinematics by significantly decreasing ATP levels in spermatozoa and increases the phosphorylation of tyrosine residues on sperm proteins involved in protein kinase A-dependent regulation thus leading to a precocious acrosome reaction. One of the metabolites of BPA is ROS, which may cause “second hit” for testicle and epididymis injury. In conclusion, BPA exposure compromises sperm production and functionality, disrupts the HPG axis balance and redox pathways resulting in a state of hypogonadotropic hypogonadism.
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