Sperm Ca2+ Signaling and Energy Pathways in basic science and ART

项目摘要摘要 不孕不育和不孕不育是严重的健康问题，影响着全球约9%的夫妇。从第一次 试管婴儿成功1978年，超过500万名婴儿使用辅助生殖技术出生 (艺术)。ART包括体外受精(IVF)、宫腔内人工授精(IUI)、 卵胞浆内单精子注射(ICSI)和胚胎移植技术。艺术是用在人类身上的，在 具有经济意义的动物。仅在人类中，试管受精和ICSI每年就被使用了大约80万次。总而言之， 物种，成功受孕的限制因素是获得良好的植入前质量 胚胎对着床和妊娠率有直接影响。获能涉及到串扰 在新陈代谢和信号通路之间。我们发现与钙离子载体孵育一小段时间 A23187[7]可以通过不育基因敲除(KO)遗传模型诱导精子的体外受精能力。我们 推测，至少在一定程度上，A23187的S效应是由于新陈代谢的变化。当精子 使用饥饿和救援方案改变代谢，我们观察到细胞内钙离子是 抬高了。这项提议有基本的和实用的目标。基本的科学目标是理解 这些方法的分子基础，特别强调钙和代谢之间的串扰 小路。在翻译层面，我们的目标是使用新的精子孵化条件来改进ART。这 支持威廉·大卫·韦伯博士职业发展的行政补充有了新的方法和 它与家长资助HD38082具有协同作用。该应用程序还将重点放在指导计划以及 提升韦伯博士的研究技能，成为一名独立研究员。

Project Summary Abstract Infertility and subfertility are critical health problems affecting about 9 % of couples worldwide. Since the first successful “Test-Tube” baby in 1978, over 5 million babies were born using Assisted Reproductive Technology (ART). ART includes such techniques as in vitro fertilization (IVF), intrauterine insemination (IUI), intracytoplasmic sperm injection (ICSI) and embryo transfer techniques. ART is used in humans, and in animals of economic relevance. In humans alone, IVF and ICSI are used ~ 800,000 times per year. In all species, the limiting factor for successful pregnancies to occur is obtaining good quality preimplantation embryos which have a direct influence in implantation and pregnancy rates. Capacitation involves crosstalk between metabolic and signaling pathways. We showed that a short incubation with the Ca2+ ionophore A23187[7] can induce in vitro fertilizing capacity in sperm from sterile knock-out (KO) genetic models. We hypothesized that, at least, in part, A23187’s effects were due to changes in metabolism. When sperm metabolism was changed using starvation and rescue protocols, we observed that intracellular Ca2+ was elevated. This proposal has basic and applied goals. The basic science objective is to understand the molecular basis of these methods with particular emphasis on the crosstalk between calcium and metabolic pathways. At the translational level, our goal is to use novel sperm incubation conditions to improve ART. This administrative supplement to support Dr. William David Weber’s career development has new approaches and it is synergic to the parent grant HD38082. The application also focuses in a mentoring plan as well as in enhancing Dr. Weber’s research skills to become an independent researcher.