The role of cholesterol efflux in regulating the fertilization potential of mammalian spermatozoa.
The role of cholesterol efflux in regulating the fertilization potential of mammalian spermatozoa.
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DOI：
10.1172/jci16392
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发表时间：
2002-09
期刊：
影响因子：
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通讯作者：
A. Travis;G. Kopf
中科院分区：
文献类型：
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作者：
A. Travis;G. Kopf
在精子发生和精子生成之后，离开睾丸的哺乳动物精子在形态上似乎是成熟的，但从功能的角度来看显然是不成熟的;也就是说，它们既没有获得前向运动能力，也没有使中期II停滞的卵子受精的能力。虽然精子在附睾中的运动是渐进的，信号通路也在精子通过附睾的过程中成熟，但体内完全受精的能力只有在精子停留在雌性生殖道时才能被赋予。使用各种体外试验也得到了类似的观察结果，表明一系列事件（有些是由环境因素引发的）赋予精子使卵子受精的能力。这种获得的受精能力首先由Austin（1）和Chang（2）观察到，他们证明了新鲜射出的精子只有在女性生殖道中停留一段有限的时间后才能使卵子受精。所有允许射出的精子使卵子受精的细胞事件都被归入一个被称为“获能”的单一现象。精子体外获能的能力对科学家和临床医生都非常重要，他们用它来研究受精的基础生物学，并为人类和其他物种开发各种辅助生殖技术。许多研究人员的工作已经确定，受精过程，毫不奇怪，代表了一系列优雅的细胞间通讯和细胞激活事件（3 - 5）。精子在女性生殖道中的运动和获能等功能可能受到腔液中的环境因素以及与输卵管上皮或其他女性组织的相互作用的调节（6）。当精子到达输卵管并遇到被包裹在其卵丘细胞基质中的排卵的中期II-停滞的卵子时，一系列复杂的细胞-细胞和细胞-ECM相互作用开始，启动允许精子和卵子质膜融合的细胞信号传导事件。这些细胞-基质和细胞-细胞相互作用中的一些涉及新的配子表面蛋白和基质。导致配子激活的信号转导事件，特别是精子顶体胞吐和卵皮质颗粒分泌，与体细胞中描述的信号转导事件有一些共同的特征。精子膜胆固醇流出有助于控制精子获能的一种新的信号传导机制，这种效应的细节现在开始在分子水平上被理解。了解胆固醇外流如何发生在这些细胞中，以及这种外流如何与跨膜信号转导整合以调节精子功能，可能会揭示很多关于受精过程的信息，也可能会提供对膜胆固醇外流在体细胞功能中的作用和动力学的见解。在此，我们对胆固醇流出在调节精子获能中的作用作一简要概述，目的是确定未来研究的领域，这些领域最终可能会促进精子获能。
Following spermatogenesis and spermiogenesis, mammalian spermatozoa leaving the testis appear to be morphologically mature but clearly are immature from a functional standpoint; that is, they have acquired neither progressive motility nor the ability to fertilize a metaphase II‐arrested egg. Although progressive motility is acquired and signaling pathways mature during sperm transit through the epididymis, complete fertilization capacity in vivo is conferred only during residence in the female reproductive tract. Similar observations have been made using a variety of in vitro assays, suggesting that a series of events, some initiated by environmental cues, confer on sperm the ability to fertilize the egg. This acquired capacity to fertilize was first observed by Austin (1) and Chang (2), who demonstrated that freshly ejaculated sperm cannot fertilize eggs until they reside in the female reproductive tract for a finite period of time. All of the cellular events that allow the ejaculated sperm to fertilize an egg were subsumed into a single phenomenon that was termed “capacitation.” The ability to capacitate sperm in vitro has been of great importance to both scientists and clinicians, who have used it to study the basic biology of fertilization and to develop various assisted reproductive technologies for humans and other species. Work by many investigators has established that the process of fertilization, not surprisingly, represents a series of elegant intercellular communication and cellular activation events (3‐5). Sperm functions such as motility and capacitation in the female reproductive tract are likely modulated by environmental cues in the luminal fluid, as well as by interactions with oviductal epithelium or other female tissues (6). When sperm arrive in the oviduct and encounter the ovulated, metaphase II‐arrested egg enclosed in its cumulus cell matrix, a complex series of cell-cell and cell-ECM interactions ensues, initiating cellular signaling events that permit the fusion of the sperm and egg plasma membranes. Several of these cell-matrix and cell-cell interactions involve novel gamete surface proteins and matrices. Signal transduction events leading to gamete activation, in particular sperm acrosomal exocytosis and egg cortical granule secretion, share some features with signaling events described in somatic cells. Sperm membrane cholesterol efflux contributes to one such novel signaling mechanism that controls sperm capacitation, and the details of this effect are now beginning to be understood at the molecular level. Knowledge of how cholesterol efflux occurs in these cells, as well as how this efflux is integrated with transmembrane signaling to regulate sperm function, may reveal much about the fertilization process and may also provide insights into the role and dynamics of membrane cholesterol efflux in somatic cell function. Here, we offer a short overview of the role of cholesterol efflux in regulating sperm capacitation, with an aim toward identifying areas of future investigation that may ultimately pro