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

项目摘要 不孕症和低生育力是严重的健康问题，影响着全世界约9%的夫妇。由于第一 1978年，超过500万婴儿通过辅助生殖技术出生 （ART）。ART包括体外受精（IVF）、子宫内授精（IUI）、 卵胞浆内单精子注射（ICSI）和胚胎移植技术。ART用于人类， 动物的经济价值。仅在人类中，IVF和ICSI每年使用约80万次。在所有 种，成功怀孕的限制因素是获得良好的植入前质量 胚胎对着床率和妊娠率有直接影响。电容涉及串扰 代谢和信号通路之间的联系。我们发现，与Ca2+离子载体的短暂孵育 A23187 [7]可以诱导来自不育基因敲除（KO）遗传模型的精子的体外受精能力。我们 假设，至少在某种程度上，A23187的作用是由于代谢的变化。当精子 使用饥饿和救援方案改变了代谢，我们观察到细胞内Ca2 + 升高。该提案有基本目标和应用目标。基础科学的目标是了解 这些方法的分子基础，特别强调钙和代谢之间的串扰 途径。在翻译水平上，我们的目标是使用新的精子孵育条件来改善ART。 支持威廉大卫韦伯博士的职业发展的行政补充有新的方法， 它与父授权HD38082协同。该应用程序还侧重于指导计划以及 提高韦伯博士的研究技能，成为一名独立的研究人员。

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.