切断促使精子移动的动力源,也可以达到避孕效果。
科学家已经找到阻止精子游动的方法,这使人们期待已久的男性避孕药距离变成现实更近一步。通过查明切断促使精子移动的动力源的方法,科学家现在已经能让精子在原地抽动,而不是游动。
澳大利亚墨尔本莫纳什大学的科学家领导的这项研究,可能为查明导致男性不育问题的原因提供了一些线索。该科研组在实验室拿老鼠进行试验期间,对老鼠体内一个名叫RABL2的基因进行了突变,该基因释放的蛋白为精子尾巴(即基因丝)里的“发动机”提供燃料。该基因突变导致精子的尾巴比正常精子短17%,并导致精子的生成量减少50%。这项研究的首席研究人员、莫纳什大学生物科学院的莫伊拉-奥比安教授称,以后的男性避孕药将会抑制RABL2基因的活性,而不是永久性改变它的活性。所有拥有这种突变基因的老鼠都不育,且精子失去游动能力。
奥比安说:“它们的行为都很正常。但是6周后并没有小老鼠诞生。所有携带这种突变基因的雄性老鼠都丧失了生育能力。研制男性避孕药面临的最大挑战不是使精子不育,而是如何重新恢复这些不育精子的受精能力。”由于身体的其他部位也有这种基因,例如脑组织、肝脏和肾组织,因此这种男性避孕药必须只对睾丸里的这种基因起作用。这项研究是该校与英国剑桥大学和纽卡斯尔大学联合进行的,研究成果发表在《公共科学图书馆—遗传学》上。以前的研究发现,55%的男性愿意服用男性避孕药。但是2010年发表研究成果的英国一项研究发现,女人不相信男人会坚持每天服用男性避孕药。正在研发的其他类型的男性避孕方法包括每月给男性注射一次的注射剂。
另外有一种男性避孕药的形式是睾酮避孕针(testosterone jab),它在臀部注射,通过调节左右大脑的化学物质,暂时阻止精子产生。中国一项为期2年的试验涉及到1000名男性,结果发现这种注射剂的避孕成功率是95%。但是有三分之一的人退出该试验,他们表示不愿忍受每月注射一次的痛苦和潜在的副作用,例如情绪波动、性欲低下和痤疮。另一个选择是服用一种能够在射精时阻止精子释放的男性避孕药。这种药物的成分在六十多岁的人服用的降压药和安定药里也能找到,研究发现,这些物质具有干射精(dry ejaculation) 的副作用。它们会麻痹男性生殖系统里的特定肌肉,导致精子释放暂时受阻,对性欲、性能力或感觉没有不良影响,因此男性仍会体验到性高潮,只是不会有精液射出。伦敦国王学院医院的研究人员进行的研究指出,这种男性避孕药会在服用3个小时内起效,药效能够持续2天,因此可以在需要时服用。
RAB-Like 2 Has an Essential Role in Male Fertility, Sperm Intra-Flagellar Transport, and Tail Assembly
Jennifer C. Y. Lo, Duangporn Jamsai, Anne E. O'Connor, Claire Borg, Brett J. Clark, James C. Whisstock, Mark C. Field, Vicki Adams, Tomomoto Ishikawa, R. John Aitken, Belinda Whittle, Christopher C. Goodnow, Christopher J. Ormandy, Moira K. O'Bryan
A significant percentage of young men are infertile and, for the majority, the underlying cause remains unknown. Male infertility is, however, frequently associated with defective sperm motility, wherein the sperm tail is a modified flagella/cilia. Conversely, a greater understanding of essential mechanisms involved in tail formation may offer contraceptive opportunities, or more broadly, therapeutic strategies for global cilia defects. Here we have identified Rab-like 2 (RABL2) as an essential requirement for sperm tail assembly and function. RABL2 is a member of a poorly characterized clade of the RAS GTPase superfamily. RABL2 is highly enriched within developing male germ cells, where it localizes to the mid-piece of the sperm tail. Lesser amounts of Rabl2 mRNA were observed in other tissues containing motile cilia. Using a co-immunoprecipitation approach and RABL2 affinity columns followed by immunochemistry, we demonstrated that within developing haploid germ cells RABL2 interacts with intra-flagella transport (IFT) proteins and delivers a specific set of effector (cargo) proteins, including key members of the glycolytic pathway, to the sperm tail. RABL2 binding to effector proteins is regulated by GTP. Perturbed RABL2 function, as exemplified by the Mot mouse line that contains a mutation in a critical protein–protein interaction domain, results in male sterility characterized by reduced sperm output, and sperm with aberrant motility and short tails. Our data demonstrate a novel function for the RABL protein family, an essential role for RABL2 in male fertility and a previously uncharacterised mechanism for protein delivery to the flagellum.