近日,日本研究人员不久前通过动物实验发现,精细胞中有一种酶,它催化合成的蛋白质是受精所必需的物质,没有这种酶,精子就无法顺利通过输卵管与卵子结合。
精细胞是动物睾丸产生的一种单倍体细胞,是由精母细胞经过两次减数分裂形成的。精细胞经过变形最终形成精子。
大阪大学特聘研究员德弘圭造和同事2月20日在美国《国家科学院院刊》网络版上报告说,他们研究了小鼠精细胞中的“PDILT”酶,然后通过基因操作,使小鼠体内不含这种酶,结果发现这种小鼠无法生成“ADAM3”蛋白质,这种物质是精子吸附到输卵管壁上并抵达卵子所必需的。
不含“PDILT”酶的小鼠能够正常交配,其精子的外观与运动能力也无异常,却无法通过雌鼠的输卵管。但如果向雌鼠输卵管内的卵子所在位置直接输入“缺酶”雄鼠的精子,雌鼠就会怀孕,说明虽然这种精子无法穿越输卵管,但它与卵子直接结合的功能正常。
大阪大学副教授伊川正人指出,不育的某些原因尚未完全明确,缺乏这种酶可能是一种原因。这一发现或许有助于开发诊断和治疗不育症的药物。
研究小组还认为,如果能开发出遏制“PDILT”酶发挥作用的物质,也可将其用于避孕。(生物谷Bioon.com)
doi:10.1073/pnas.1117963109
PMC:
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.