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Sperm Ca2+ signaling and energy pathways in basic science and ART

基础科学和 ART 中的精子 Ca2 信号传导和能量途径

基本信息

批准号：
10398801
负责人：
Pablo E. Visconti
金额：
$ 42.91万
依托单位：
UNIVERSITY OF MASSACHUSETTS AMHERST
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10398801
关键词：
Affect Age Animals Artificial Insemination Assisted Reproductive Technology Back Basic Science Bypass Calcium Cell division Couples Data Development Economics Embryo Embryo Transfer Embryonic Development Environmental Risk Factor Event Exposure to Female Fertilization Fertilization in Vitro Gene Expression Genetic Genetic Models Germ Cells Glycolysis Goals Health Human Implant In Vitro Incubated Individual Infertility Intracytoplasmic Sperm Injections Ionophores Knock-out Mammals Mediating Metabolic Metabolic Pathway Metabolism Methodology Methods Molecular Nutrient Obesity Output Oxidative Phosphorylation Pathway interactions Phosphorylation Physiological Pregnancy Pregnancy Rate Procedures Process Protocols documentation Publishing Recovery Regulation Signal Pathway Signal Transduction Site Sperm Motility Starvation Sterility Techniques Test-Tube Baby Testing Time Translating Uterus base blastocyst calcium metabolism cell motility design egg experience experimental study genetic approach human disease human model implantation improved insight intrauterine insemination metabolomics mouse model novel offspring pregnant programs pup reproductive tract response spatiotemporal sperm cell sperm cryopreservation sperm function subfertility tool zygote

项目摘要

Project Summary 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. In the previous period, 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. In addition, we found that, similar to A23187, sperm incubated in the absence of nutrients become immotile. Once nutrients are added back to the incubation media, sperm motility is rescued and those sperm depict higher percentage of hyperactivation and enhanced in vitro fertilization (IVF) rates. Unexpectedly, eggs fertilized with sperm incubated in metabolic enhanced conditions were more efficient in producing blastocysts and those blastocysts generated more implantation sites and produced more pups when transferred to pseudo-pregnant females. 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.

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。在上一节课中，我们展示了一个短暂的孵化， Ca2+离子载体A23187[7]可以诱导不育基因敲除（KO）的精子体外受精能力模型我们假设，A23187的作用至少部分是由于代谢的变化。当采用饥饿和拯救方案改变精子代谢，我们观察到细胞内Ca2+ 升高。此外，我们发现，与A23187类似，在缺乏营养的情况下孵育的精子变得更容易存活。一动不动一旦营养物质被添加回孵育培养基，精子活力被拯救，显示了更高的超活化百分比和增强的体外受精（IVF）率。出乎意料的是，鸡蛋与在代谢增强条件下孵育的精子受精的小鼠在产生囊胚方面更有效这些胚泡产生了更多的植入位点，当转移到假怀孕的女性该提案有基本目标和应用目标。基本科学目标是理解这些方法的分子基础，特别强调钙离子之间的串扰和代谢途径。在翻译水平上，我们的目标是使用新的精子孵育条件，改善艺术。