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PNAS:小鼠研究为男性避孕药的开发提供依据

  1. 小鼠
  2. 避孕药

来源:生物谷 2013-12-05 11:14

澳大利亚科学家成功使雄性小鼠不育,该发现为男性避孕药的发明提供了重要依据

2013年12月5日讯 /生物谷BIOON/--近期发表在PNAS杂志上的文章称,澳大利亚科学家成功使雄性小鼠不育,该发现为男性避孕药的发明提供了重要依据。

莫纳什大学科学家采用基因工程手段抑制小鼠平滑肌上的两个蛋白的功能,该蛋白在精子穿过生殖器官的过程中起重要作用。抑制蛋白功能结果使得雄性小鼠不育,但是雄鼠的性能力和其他功能正常。

Ventura博士称,我们发现破坏两个控制精子转移的关键蛋白就能够使得雄性小鼠不育,而该操作不会影响精子的长时间的生存能力或雄性的生殖器官的能力。

Ventura博士补充道,我们下一步打算开发口服男性避孕药,希望该药具有高效、安全且可恢复的特点。

而之前开发男性避孕药的研究都是集中在激素或使精子功能异常方面,这些都会引起长期或潜在的危害。(生物谷Bioon.com)

doi: 10.1073/pnas.1318624110

Male contraception via simultaneous knockout of α1A-adrenoceptors and P2X1-purinoceptors in mice

Carl W. White, Yan-Ting Choong, Jennifer L. Short, Betty Exintaris, Daniel T. Malone, Andrew M. Allen, Richard J. Evans, and Sabatino Ventura

Therapeutic targets for male contraception are associated with numerous problems due to their focus on disrupting spermatogenesis or hormonal mechanisms to produce dysfunctional sperm. Here we describe the dual genetic deletion of α1A-adrenergic G protein-coupled receptors (adrenoceptors) and P2X1-purinoceptor ligand gated ion channels in male mice, thereby blocking sympathetically mediated sperm transport through the vas deferens during the emission phase of ejaculation. This modification produced 100% infertility without effects on sexual behavior or function. Sperm taken from the cauda epididymides of double knockout mice were microscopically normal and motile. Furthermore, double knockout sperm were capable of producing normal offspring following intracytoplasmic sperm injection into wild-type ova and implantation of the fertilized eggs into foster mothers. Blood pressure and baroreflex function was reduced in double knockout mice, but no more than single knockout of α1A-adrenoceptors alone. These results suggest that this autonomic method of male contraception appears free of major physiological and behavioral side effects. In addition, they provide conclusive proof of concept that pharmacological antagonism of the P2X1-purinoceptor and α1A-adrenoceptor provides a safe and effective therapeutic target for a nonhormonal, readily reversible male contraceptive.

 

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