近日，日本研究人員不久前通過(guò)動(dòng)物實(shí)驗(yàn)發(fā)現(xiàn),，精細(xì)胞中有一種酶,，它催化合成的蛋白質(zhì)是受精所必需的物質(zhì)，沒(méi)有這種酶,，精子就無(wú)法順利通過(guò)輸卵管與卵子結(jié)合,。
精細(xì)胞是動(dòng)物睪丸產(chǎn)生的一種單倍體細(xì)胞，是由精母細(xì)胞經(jīng)過(guò)兩次減數(shù)分裂形成的,。精細(xì)胞經(jīng)過(guò)變形最終形成精子,。
大阪大學(xué)特聘研究員德弘圭造和同事2月20日在美國(guó)《國(guó)家科學(xué)院院刊》網(wǎng)絡(luò)版上報(bào)告說(shuō)，他們研究了小鼠精細(xì)胞中的“PDILT”酶,，然后通過(guò)基因操作,，使小鼠體內(nèi)不含這種酶，結(jié)果發(fā)現(xiàn)這種小鼠無(wú)法生成“ADAM3”蛋白質(zhì),，這種物質(zhì)是精子吸附到輸卵管壁上并抵達(dá)卵子所必需的。
不含“PDILT”酶的小鼠能夠正常交配,，其精子的外觀與運(yùn)動(dòng)能力也無(wú)異常,，卻無(wú)法通過(guò)雌鼠的輸卵管。但如果向雌鼠輸卵管內(nèi)的卵子所在位置直接輸入“缺酶”雄鼠的精子,，雌鼠就會(huì)懷孕,，說(shuō)明雖然這種精子無(wú)法穿越輸卵管，但它與卵子直接結(jié)合的功能正常,。
大阪大學(xué)副教授伊川正人指出,，不育的某些原因尚未完全明確，缺乏這種酶可能是一種原因,。這一發(fā)現(xiàn)或許有助于開(kāi)發(fā)診斷和治療不育癥的藥物,。
研究小組還認(rèn)為，如果能開(kāi)發(fā)出遏制“PDILT”酶發(fā)揮作用的物質(zhì),，也可將其用于避孕,。（生物谷Bioon.com）
doi:10.1073/pnas.1117963109
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PMID:
Protein disulfide isomerase homolog PDILT is required for quality control of sperm membrane protein ADAM3 and male infertility
Keizo Tokuhiroa, Masahito Ikawaa,1, Adam M. Benhama,b, and Masaru Okabea,c,d
A disintegrin and metalloproteinase 3 (ADAM3) is a sperm membrane protein critical for both sperm migration from the uterus into the oviduct and sperm primary binding to the zona pellucida (ZP). Here we show that the testis-specific protein disulfide isomerase homolog (PDILT) cooperates with the testis-specific calreticulin-like chaperone, calsperin (CALR3), in the endoplasmic reticulum and plays an indispensable role in the disulfide-bond formation and folding of ADAM3. Pdilt−/− mice were male infertile because ADAM3 could not be folded properly and transported to the sperm surface without the PDILT/CALR3 complex. Peculiarly we find that not only Pdilt−/−, but also Adam3−/−, spermatozoa effectively fertilize eggs when the eggs are surrounded in cumulus oophorus. These findings reveal that ADAM3 requires testis-specific private chaperones to be folded properly and that the principle role of ADAM3 is for sperm migration into the oviduct but not for the fertilization event. Moreover, the importance of primary sperm ZP binding, which has been thought to be a critical step in mammalian fertilization, should be reconsidered.
