Physiological studies of sperm from normal and sub fertile men

正常和生育力低下男性精子的生理学研究

• 批准号: MR/K013343/2
• 负责人: Stuart Wilson
• 金额: $ 47.78万
• 依托单位: Durham University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK013343%2F2
• 关键词: Physiological; studies; sperm; normal; sub

Men produce approximately 1000 sperm in every heartbeat. The main job of the sperm cell is to reach and fertilise the egg. However, we know very little about the journey the sperm makes in the female tract but we do know it must survive for up to 6 days and successfully navigate to the egg and 'drill' its entry path through the tough envelope that surrounds it. Success in this venture requires the deployment of strikingly different movement (motility) patterns which are controlled by the female reproductive tract through a series of finely tuned (but very poorly understood) stop/start signals. One key way the female tract communicates with the sperm is to manipulate the calcium level in a cell which then changes the way the cell moves. Surprisingly there are a large number of men (1:15) who produce sperm but their cells do not function in an optimal way. Such men have difficulties getting their partner pregnant. A primary cause of the sperm not working well is that they do not swim in the same manner as normal cells and a reason for this is that they have an abnormal calcium response to female reproductive tract signals. We do not know why these sperm have poor calcium responses. Very recently a specialised technique which allows us to obtain critical information on each sperm has been developed (patch clamping). This technique allows us to examine how calcium is changes in the sperm cell. We will use this specialised technique to study sperm from men with abnormalities and compare them to normal men. We anticipate that this will allow us to determine, for the first time, what are the specific problems in calcium regulation in sperm cells from men with fertility problems. If we can identify these problems it is possible that in the future we may be able to develop drugs to treat these abnormal cells and, conversely perhaps interrupt the calcium pathways in normal cells to develop a new male contraceptive.

男性在每个心跳中产生大约1000个精子。精子细胞的主要工作是达到和施肥卵。但是，我们对精子在雌性区域的旅程知之甚少，但我们确实知道它必须生存长达6天，并成功地导航到鸡蛋并“钻”其入口路径，穿过周围的艰难信封。在该合资企业中的成功需要部署明显不同的运动（运动）模式，这些模式由女性生殖道控制，通过一系列细微的调谐（但非常了解）停止/启动信号。女性道与精子通信的一种关键方式是操纵细胞中的钙水平，然后改变细胞的移动方式。令人惊讶的是，有大量男性（1:15）产生精子，但其细胞无法以最佳方式发挥作用。这样的人很难怀孕。精子无法正常工作的主要原因是，它们的游泳方式与正常细胞不相同，原因是它们对女性生殖道信号的钙反应异常。我们不知道为什么这些精子的钙反应较差。最近，一种专门的技术，使我们能够获得有关每个精子的关键信息（补丁夹）。该技术使我们能够检查精子细胞中钙的变化。我们将使用这种专业技术来研究异常男性的精子，并将其与普通男性进行比较。我们预计这将使我们能够首次确定生育能力问题的精子细胞中钙调节中的特定问题。如果我们能确定这些问题，将来有可能能够开发药物来治疗这些异常细胞，相反，也许会中断正常细胞中的钙途径以开发新的雄性避孕药。

项目成果

Specific loss of CatSper function is sufficient to compromise fertilizing capacity of human spermatozoa.

• DOI: 10.1093/humrep/dev243
• 发表时间: 2015-12
• 期刊: Human reproduction (Oxford, England)
• 作者: Williams HL;Mansell S;Alasmari W;Brown SG;Wilson SM;Sutton KA;Miller MR;Lishko PV;Barratt CL;Publicover SJ;Martins da Silva S
• 通讯作者: Martins da Silva S

Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF.

• DOI: 10.1093/humrep/dew056
• 发表时间: 2016-06
• 期刊: Human reproduction (Oxford, England)
• 作者: Brown SG;Publicover SJ;Mansell SA;Lishko PV;Williams HL;Ramalingam M;Wilson SM;Barratt CL;Sutton KA;Da Silva SM
• 通讯作者: Da Silva SM

p,p'-DDE activates CatSper and compromises human sperm function at environmentally relevant concentrations.

• DOI: 10.1093/humrep/det372
• 发表时间: 2013-12
• 期刊: Human reproduction (Oxford, England)
• 作者: Tavares RS;Mansell S;Barratt CL;Wilson SM;Publicover SJ;Ramalho-Santos J
• 通讯作者: Ramalho-Santos J

A spontaneous increase in intracellular Ca2+ in metaphase II human oocytes in vitro can be prevented by drugs targeting ATP-sensitive K+ channels.

• DOI: 10.1093/humrep/dev300
• 发表时间: 2016-02
• 期刊: Human reproduction (Oxford, England)
• 作者: Fernandes G;Dasai N;Kozlova N;Mojadadi A;Gall M;Drew E;Barratt E;Madamidola OA;Brown SG;Milne AM;Martins da Silva SJ;Whalley KM;Barratt CL;Jovanović A
• 通讯作者: Jovanović A

Patch clamp studies of human sperm under physiological ionic conditions reveal three functionally and pharmacologically distinct cation channels.

• DOI: 10.1093/molehr/gau003
• 发表时间: 2014-05
• 期刊: Molecular human reproduction
• 影响因子: 4
• 作者: Mansell SA;Publicover SJ;Barratt CL;Wilson SM
• 通讯作者: Wilson SM