Fraser Lynn R, Beyret Ergin, Milligan Stuart R, Adeoya-Osiguwa Susan A
Reproduction and Rhythms Group, School of Biomedical and Health Sciences, King's College London, London, UK.
Hum Reprod. 2006 May;21(5):1184-93. doi: 10.1093/humrep/dei486. Epub 2006 Feb 3.
To investigate human sperm responsiveness to the estrogenic xenobiotic genistein and seek further information regarding the mechanism of action of estrogenic xenobiotics using mouse spermatozoa.
Uncapacitated human spermatozoa were incubated with genistein and assessed using chlortetracycline (CTC) fluorescence. CTC was also used to evaluate mouse sperm responses to daidzein and combinations of genistein, 8-prenylnaringenin and nonylphenol. Several steroids were tested to determine structure-function relationships, and possible involvement of cAMP and G proteins in responses was also investigated.
Genistein significantly accelerated capacitation and acrosome loss in human spermatozoa, with 1, 10 and 100 nmol/l being equally effective. In mouse spermatozoa, daidzein produced significant responses, and combinations of xenobiotics at low concentrations were more effective than used singly. The compounds appear to act at the cell surface, and responses to three different steroids were nonidentical. A protein kinase-A inhibitor blocked responses to xenobiotics, while genistein and nonylphenol significantly stimulated cAMP production. Pertussis toxin and dideoxyadenosine blocked responses, suggesting involvement of inhibitory G proteins and membrane-associated adenylyl cyclases.
Human and mouse sperm responses to genistein are very similar, but human gametes appear to be even more sensitive. The mechanism of action may involve unregulated stimulation of cAMP production, leading to significant acrosome loss, undesirable because already acrosome-reacted cells are nonfertilizing. Xenobiotics were even more effective in combination. Since simultaneous exposure to low concentrations of multiple xenobiotics is likely to occur in animals and humans, further investigation is needed to determine whether this could impair fertility.
研究人类精子对雌激素样外源性物质染料木黄酮的反应，并利用小鼠精子进一步探寻雌激素样外源性物质的作用机制。
将未获能的人类精子与染料木黄酮共同孵育，并用金霉素（CTC）荧光法进行评估。CTC还用于评价小鼠精子对黄豆苷元以及染料木黄酮、8-异戊烯基柚皮素和壬基酚组合的反应。测试了几种甾体以确定结构-功能关系，同时还研究了环磷酸腺苷（cAMP）和G蛋白在反应中可能的参与情况。
染料木黄酮显著加速了人类精子的获能和顶体丢失，1、10和100纳摩尔/升的效果相同。在小鼠精子中，黄豆苷元产生了显著反应，低浓度外源性物质的组合比单独使用更有效。这些化合物似乎作用于细胞表面，对三种不同甾体的反应并不相同。蛋白激酶A抑制剂可阻断对外源性物质的反应，而染料木黄酮和壬基酚可显著刺激cAMP的产生。百日咳毒素和双脱氧腺苷可阻断反应，提示抑制性G蛋白和膜相关腺苷酸环化酶的参与。
人类和小鼠精子对染料木黄酮的反应非常相似，但人类配子似乎更敏感。作用机制可能涉及对cAMP产生的无节制刺激，导致显著的顶体丢失，这是不理想的，因为已经发生顶体反应的细胞无法受精。外源性物质组合的效果甚至更佳。由于动物和人类可能同时接触低浓度的多种外源性物质，因此需要进一步研究以确定这是否会损害生育能力。
