福音：光激活精子可帮助男性恢复生育能力

科学家们使用光脉冲来控制精子功能,不仅使之前无活力的精子鞭毛开始有活力的运动,而且使不育小鼠恢复生育能力。科学家们通过光遗传学的应用程序获得现有成果,光遗传学包括为光敏蛋白质编码所插入的基因。

到目前为止,光遗传学一直是最突出的神经科学,光敏离子通道被用来控制神经细胞的电子活性。光遗传学的用途现在越来越广泛。当前研究表明,光遗传学可用于打开或关闭细胞中信号通路。

欧洲高级研究中心(CAESAR)的科学家在缺乏内源性酶的小鼠中插入一个表达光敏化的腺苷酸环化酶的基因。这些小鼠的精子通常无活性,小鼠因此不育。蓝光伪装了这些精子后生产环磷酸腺苷(cAMP),之后精子开始有活力,甚至能使卵子受精。

研究结果在发表在1月20日《eLife》杂志上，题为“控制受精并通过光遗传学使环磷酸腺苷在精子中发出信号”。

光激活的腺苷酸环化酶早期被发现在土壤中的细菌中，因此该酶的简称为bPAC,为细菌使光敏化腺苷酸环化酶。在转基因精子中,bPAC模拟内源性可溶性腺苷酸环化酶(SACY)的作用，该酶是精子能动性和受精作用的必需物质。

“光刺激可迅速提升环磷酸腺苷的产量,加快了鞭毛运动,从而改变了精子的活性,”研究者说，“此外,bPAC代替了内源性腺苷酸环化酶活性作用。突变体精子缺乏重碳酸盐刺激的内源性可溶性腺苷酸环化酶活性,bPAC在光刺激后可恢复能动性,从而使精子与卵母细胞体外受精”。

腺苷酸环化酶合成cAMP,它是重要的细胞信使。cAMP控制心率、嗅觉,学习,记忆形成,受精等功能。光遗传学影响腺苷酸环化酶的水平,以及cAMP水平,CAESAR的科学家表明,光遗传学可控制单个细胞的行为,并恢复基本生物受精过程。

科学家们指出,光遗传学扩大了光活性磷酸二酯酶(LAPD)，并通过红光刺激环核苷酸水解该酶。“光活性磷酸二酯酶和带有荧光性cAMP生物传感器的bPAC可以帮助绘制活细胞中cAMP的动态信号图谱,”他们解释说。“这些发现鼓励在未来的研究方向上能够发掘探索光遗传学控制细胞信使的潜能。”（转化医学网360zhyx.com）

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附原文：

By using pulses of light to control sperm function, scientists have not only induced vigorous beating in formerly listless flagella, they have also restored fertility to once sterile mice. The scientists achieved all this through an application of optogenetics, which involves the insertion of genes that code for light-sensitive proteins.

To date, optogenetics has been most prominent in the neurosciences, where light-sensitive ion channels are used to control the electrical activity of nerve cells. But optogenetics is becoming more versatile. As the current study demonstrates, optogenetics can be used to switch messenger-mediated signaling pathways in cells on and off.

Scientists from the Center of Advanced European Studies and Research (caesar) inserted a gene expressing a photoactivated adenylyl cyclase into mice that lacked the endogenous enzyme. Sperm of these mice are usually non-motile, and the mice consequently infertile. After simulation of these sperm with blue light, they produce cyclic AMP (cAMP), start to swim again, and are even able to fertilize eggs.

These results were reported January 20 in the journal eLife, in an article entitled “Controlling fertilization and cAMP signaling in sperm by optogenetics.”

The light-activated adenylyl cyclase had been discovered earlier in soil bacteria—hence the enzyme’s acronym bPAC, for bacterial photoactivated adenylate cyclase. In transgenic sperm, bPAC mimics the action of the endogenous soluble adenylyl cyclase (SACY) that is required for motility and fertilization.

“Light-stimulation rapidly elevates cAMP, accelerates the flagellar beat, and thereby changes swimming behavior of sperm,” wrote the authors of the eLife article. “Furthermore, bPAC replaces endogenous adenylyl cyclase activity. In mutant sperm lacking the bicarbonate-stimulated SACY activity, bPAC restored motility after light-stimulation and, thereby, enabled sperm to fertilize oocytes in vitro.”

The enzymes known as adenylate cyclases synthesize cAMP, an important cellular messenger. cAMP controls a wide range of functions such as heart rate, the sense of smell, learning, memory formation, and the fertilization of eggs. By optogenetically influencing adenylate cyclase levels, and thereby cAMP levels, the caesar scientists have shown that it is possible to control the behaviors of single cells, and to restore a fundamental biological process such as fertilization.

Anticipating future work, the scientists noted that the optogenetic toolkit has been recently expanded by a light-activated phosphodiesterase (LAPD) that hydrolyses cyclic nucleotides upon stimulation by red light. “A combination of LAPD and bPAC with fluorescent cAMP biosensors holds great promise to map the dynamics of cAMP signaling in live cells in precise spatio-temporal and quantitative terms,” they explained. “These findings encourage future studies to explore the full potential of controlling cellular messengers by optogenetics.”