英國(guó)劍橋大學(xué)和澳大利亞莫納什大學(xué)的研究人員稱,，他們從基因角度找到一種阻止精子游泳的方法，有望在掌握一種新的男性避孕藥方面獲得關(guān)鍵性突破,。這項(xiàng)研究結(jié)果刊登在最新一期《公共科學(xué)圖書館—遺傳學(xué)》雜志上,。
從世界范圍看，采取避孕措施的人口中,，八成以上是女性絕育和使用宮內(nèi)節(jié)育器,，男性絕育只占9.2%。在藥物避孕人群中,，也主要由女性服用避孕藥物,。而采取男性避孕措施的人口數(shù)量之所以偏低，主要是因?yàn)槟壳吧形撮_(kāi)發(fā)出絕對(duì)安全的男性避孕藥,。
領(lǐng)導(dǎo)這項(xiàng)研究的莫納什大學(xué)教授莫伊拉表示,，他們?cè)谝豁?xiàng)更好地了解男性不育的研究中發(fā)現(xiàn),，當(dāng)小鼠的一個(gè)特定基因副本突變后，其產(chǎn)生精子的尾巴會(huì)短17%,，導(dǎo)致它們游泳能力驟降,。該基因稱為RABL2，其會(huì)比正常副本導(dǎo)致小鼠產(chǎn)精量減少50%,。莫伊拉說(shuō)：“當(dāng)RABL2基因突變,，很容易造成不育。此外,，精子的運(yùn)動(dòng)性對(duì)于男性的生育能力是絕對(duì)必要的,，洞察精子尾部的功能可能會(huì)開(kāi)發(fā)出基于男性的緊急避孕藥物。”
進(jìn)一步的研究表明,，該基因產(chǎn)生稱為鞭毛內(nèi)傳輸?shù)牡鞍踪|(zhì),，這種蛋白質(zhì)與其他分子相互作用，不斷加長(zhǎng)精子的尾部以承載遺傳信息,。研究人員珍妮·弗羅說(shuō)：“數(shù)據(jù)表明,，如果RABL2功能障礙，就意味著承載到精子尾部的信息有缺陷,。而且由于RABL2不正常,，精子尾部承載的信息也會(huì)減少。最終導(dǎo)致精子的生成和活力異常,。”
由于基因突變導(dǎo)致精子數(shù)量減少,，并且妨礙其游動(dòng)能力，由此,，科學(xué)家希望可以開(kāi)發(fā)出一種避孕藥,，以降低其產(chǎn)生蛋白質(zhì)的水平。但是,，由于這種蛋白質(zhì)在身體其他部位被發(fā)現(xiàn)少量存在,，包括大腦、腎臟和肝臟之中,，未來(lái)的這類藥物還將對(duì)相關(guān)安全性展開(kāi)評(píng)估,。（生物谷Bioon.com）
doi: 10.1371/journal.pgen
PMC:
PMID:
RAB-Like 2 Has an Essential Role in Male Fertility, Sperm Intra-Flagellar Transport, and Tail Assembly
Lo JC, Jamsai D, O'Connor AE, Borg C, Clark BJ, Whisstock JC, Field MC, Adams V, Ishikawa T, Aitken RJ, Whittle B, Goodnow CC, Ormandy CJ, O'Bryan MK.
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
