PDF(Pubmed)
Abstract：
BACKGROUND: Exposure of humans and animals to heavy metals is increasing day-by-day; thus, lead even today remains of significant public health concern. According to CDC, blood lead reference value (BLRV) ranges from 3.5 µg/dl to 5 μg/dl in adults. Recently, almost 2.6% decline in male fertility per year has been reported but the cause is not well established. Lead (Pb2+) affects the size of testis, semen quality, and secretory functions of prostate. But the molecular mechanism(s) of lead toxicity in sperm cells is not clear. Thus, present study was undertaken to evaluate the adverse effects of lead acetate at environmentally relevant exposure levels (0.5, 5, 10 and 20 ppm) on functional and molecular dynamics of spermatozoa of bucks following in vitro exposure for 15 min and 3 h.
RESULTS: Lead significantly decreased motility, viable count, and motion kinematic patterns of spermatozoa like curvilinear velocity, straight-line velocity, average path velocity, beat cross frequency and maximum amplitude of head lateral displacement even at 5 ppm concentration. Pb2+ modulated intracellular cAMP and Ca2+ levels in sperm cells through L-type calcium channels and induced spontaneous or premature acrosome reaction (AR) by increasing tyrosine phosphorylation of sperm proteins and downregulated mitochondrial transmembrane potential. Lead significantly increased DNA damage and apoptosis as well. Electron microscopy studies revealed Pb2+ -induced deleterious effects on plasma membrane of head and acrosome including collapsed cristae in mitochondria.
CONCLUSIONS: Pb2+ not only mimics Ca2+ but also affects cellular targets involved in generation of cAMP, mitochondrial transmembrane potential, and ionic exchange. Lead seems to interact with Ca2+ channels because of charge similarity and probably enters the sperm cell through these channels and results in hyperpolarization. Our findings also indicate lead-induced TP and intracellular Ca2+ release in spermatozoa which in turn may be responsible for premature acrosome exocytosis which is essential feature of capacitation for fertilization. Thus, lead seems to reduce the fertilizing capacity of spermatozoa even at 0.5 ppm concentrations.
RESULTS: Lead significantly decreased motility, viable count, and motion kinematic patterns of spermatozoa like curvilinear velocity, straight-line velocity, average path velocity, beat cross frequency and maximum amplitude of head lateral displacement even at 5 ppm concentration. Pb2+ modulated intracellular cAMP and Ca2+ levels in sperm cells through L-type calcium channels and induced spontaneous or premature acrosome reaction (AR) by increasing tyrosine phosphorylation of sperm proteins and downregulated mitochondrial transmembrane potential. Lead significantly increased DNA damage and apoptosis as well. Electron microscopy studies revealed Pb2+ -induced deleterious effects on plasma membrane of head and acrosome including collapsed cristae in mitochondria.
CONCLUSIONS: Pb2+ not only mimics Ca2+ but also affects cellular targets involved in generation of cAMP, mitochondrial transmembrane potential, and ionic exchange. Lead seems to interact with Ca2+ channels because of charge similarity and probably enters the sperm cell through these channels and results in hyperpolarization. Our findings also indicate lead-induced TP and intracellular Ca2+ release in spermatozoa which in turn may be responsible for premature acrosome exocytosis which is essential feature of capacitation for fertilization. Thus, lead seems to reduce the fertilizing capacity of spermatozoa even at 0.5 ppm concentrations.
摘要：
背景：人类和动物对重金属的暴露日益增加；因此，即使在今天，铅仍然是重大的公共卫生问题。根据CDC,成人血铅参考值(BLRV)范围为3.5µg/dl至5µg/dl.最近,据报道，男性生育率每年下降近2.6%，但原因尚不明确。铅（Pb2+）影响睾丸的大小，精液质量,和前列腺的分泌功能。但铅对精子细胞毒性的分子机制尚不清楚。因此，本研究旨在评估环境相关暴露水平（0.5、5、10和20ppm）下乙酸铅对体外暴露15分钟和3小时后雄鹿精子功能和分子动力学的不利影响。
结果：铅显著降低运动能力，可行计数，和精子的运动运动学模式，如曲线速度，直线速度,平均路径速度，即使在5ppm浓度下，节拍交叉频率和头部横向位移的最大振幅。Pb2通过L型钙通道调节精子细胞内cAMP和Ca2水平，并通过增加精子蛋白的酪氨酸磷酸化和下调线粒体跨膜电位来诱导自发或过早的顶体反应（AR）。铅显著增加DNA损伤和细胞凋亡。电子显微镜研究显示，Pb2诱导的对头部和顶体的质膜的有害作用，包括线粒体中塌陷的cr。
结论：Pb2+不仅模拟Ca2+，而且影响参与cAMP生成的细胞靶标，线粒体跨膜电位，和离子交换。由于电荷相似性，铅似乎与Ca2通道相互作用，并且可能通过这些通道进入精子细胞并导致超极化。我们的发现还表明，精子中铅诱导的TP和细胞内Ca2释放，这反过来可能是过早的顶体胞吐的原因，这是受精获能的基本特征。因此，即使在0.5ppm浓度下，铅似乎也会降低精子的受精能力。
结果：铅显著降低运动能力，可行计数，和精子的运动运动学模式，如曲线速度，直线速度,平均路径速度，即使在5ppm浓度下，节拍交叉频率和头部横向位移的最大振幅。Pb2通过L型钙通道调节精子细胞内cAMP和Ca2水平，并通过增加精子蛋白的酪氨酸磷酸化和下调线粒体跨膜电位来诱导自发或过早的顶体反应（AR）。铅显著增加DNA损伤和细胞凋亡。电子显微镜研究显示，Pb2诱导的对头部和顶体的质膜的有害作用，包括线粒体中塌陷的cr。
结论：Pb2+不仅模拟Ca2+，而且影响参与cAMP生成的细胞靶标，线粒体跨膜电位，和离子交换。由于电荷相似性，铅似乎与Ca2通道相互作用，并且可能通过这些通道进入精子细胞并导致超极化。我们的发现还表明，精子中铅诱导的TP和细胞内Ca2释放，这反过来可能是过早的顶体胞吐的原因，这是受精获能的基本特征。因此，即使在0.5ppm浓度下，铅似乎也会降低精子的受精能力。
