大多數(shù)哺乳動物雄性與雌雄生殖道之間存在一個天然的滲透壓差（以小鼠為例：雄性附睪~415 mOsm, 雌性子宮~310 mOsm）,。精子從雄性生殖道進(jìn)入雌性生殖道，經(jīng)歷了一個生理狀態(tài)下的“低滲應(yīng)激”,。這種應(yīng)激一方面有利于激活精子運動（從進(jìn)化上保留了魚類精子的特征）,，但低滲環(huán)境同時也是一把“雙刃劍”，可導(dǎo)致精子細(xì)胞過度腫脹對其功能產(chǎn)生潛在傷害,。為了消除低滲導(dǎo)致的負(fù)面影響,，精子在進(jìn)化中形成了一套高效的液體調(diào)節(jié)系統(tǒng)以應(yīng)對這種生理性“低滲應(yīng)激”導(dǎo)致的細(xì)胞腫脹。然而,，在此過程中起關(guān)鍵作用的精子蛋白尚未被發(fā)現(xiàn),。
動物研究所段恩奎研究組與浙江省醫(yī)學(xué)科學(xué)院石其賢教授，吉林大學(xué)白求恩第二醫(yī)院麻彤輝教授合作研究發(fā)現(xiàn)：一個水通道蛋白（AQP3）在小鼠和人的精子尾部呈現(xiàn)特異的細(xì)胞膜定位,。AQP3缺陷的精子在進(jìn)入雌性生殖道后,，雖然能夠?qū)崿F(xiàn)運動激活,，但很快表現(xiàn)出大量精子尾部發(fā)生彎曲變形。滲透壓梯度實驗及精子游動中實時錄像監(jiān)測等手段進(jìn)一步證實,，AQP3缺陷精子對低滲導(dǎo)致的細(xì)胞膨脹抵御能力下降,，在相對低滲的雌性生殖道環(huán)境中發(fā)生細(xì)胞膜進(jìn)行性膨脹，進(jìn)而對精子尾部產(chǎn)生機(jī)械性牽張并最終導(dǎo)致尾部變形,。體內(nèi)外功能實驗表明,，由于存在尾部缺陷，大量AQP3敲除鼠精子不能有效地穿越子宮-輸卵管結(jié)合處狹部,，導(dǎo)致精子進(jìn)入輸卵管與卵子相遇的機(jī)會降低,，從而表現(xiàn)出雄性小鼠生育力下降。
Figure.1 Immunofluorescence staining of AQP3 (green signal) reveals intensive localization at principal piece of mouse and human sperm tail.
Figure.2 Time-lapse imaging reveals sperm tail bending (Aqp3 null sperm) process forced by progressive membrane expansion upon physiological hypotonic stress. The cell swelling begins at cytoplasmic droplet (indicated by arrows). Note the wildtype sperm only shows mild swelling.
此研究首次揭示了AQP3是精子在雌性生殖道中實現(xiàn)低滲適應(yīng)的一個關(guān)鍵蛋白,，在“低滲應(yīng)激”介導(dǎo)的精子運動激活和細(xì)胞過度腫脹這一對利弊權(quán)衡（trade-off）中起到消除負(fù)面影響的作用,，從而最大優(yōu)化精子功能。鑒于AQP3在人精子中的表達(dá)與小鼠呈現(xiàn)相同模式,，其在男性不育/低生育力患者中的作用尚待進(jìn)一步研究,。
本研究于12月7日在線發(fā)表于Cell research。本研究得到了國家“發(fā)育與生殖”重大科學(xué)研究計劃和中國科學(xué)院知識創(chuàng)新方向性項目資助,。（生物谷Bioon.com）
生物谷推薦原文出處：
Cell Res. doi:10.1038/cr.2010.169
Aquaporin3 is a sperm water channel essential for postcopulatory sperm osmoadaptation and migration.
Chen Q, Peng H, Lei L, Zhang Y, Kuang H, Cao Y, Shi QX, Ma T, Duan E.
[1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] Graduate School of Chinese Academy of Sciences, Beijing 100049, China.
Abstract
In the journey from the male to female reproductive tract, mammalian sperm experience a natural osmotic decrease (e.g., in mouse, from ～415 mOsm in the cauda epididymis to ～310 mOsm in the uterine cavity). Sperm have evolved to utilize this hypotonic exposure for motility activation, meanwhile efficiently silence the negative impact of hypotonic cell swelling. Previous physiological and pharmacological studies have shown that ion channel-controlled water influx/efflux is actively involved in the process of sperm volume regulation; however, no specific sperm proteins have been found responsible for this rapid osmoadaptation. Here, we report that aquaporin3 (AQP3) is a sperm water channel in mice and humans. Aqp3-deficient sperm show normal motility activation in response to hypotonicity but display increased vulnerability to hypotonic cell swelling, characterized by increased tail bending after entering uterus. The sperm defect is a result of impaired sperm volume regulation and progressive cell swelling in response to physiological hypotonic stress during male-female reproductive tract transition. Time-lapse imaging revealed that the cell volume expansion begins at cytoplasmic droplet, forcing the tail to angulate and form a hairpin-like structure due to mechanical membrane stretch. The tail deformation hampered sperm migration into oviduct, resulting in impaired fertilization and reduced male fertility. These data suggest AQP3 as an essential membrane pathway for sperm regulatory volume decrease (RVD) that balances the "trade-off" between sperm motility and cell swelling upon physiological hypotonicity, thereby optimizing postcopulatory sperm behavior.
