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.

项目概要不孕不育和生育能力低下是影响全球约 9% 夫妇的严重健康问题。 1978年“试管婴儿”成功，超过500万婴儿使用辅助生殖技术出生 (ART) 包括体外受精 (IVF)、宫内人工授精 (IUI) 等技术。胞浆内单精子注射 (ICSI) 和胚胎移植技术用于人类和其他领域。仅在人类中，每年就使用 IVF 和 ICSI 约 800,000 次。物种，成功怀孕的限制因素是获得高质量的植入前对植入率和妊娠率有直接影响的胚胎涉及串扰。在上一时期，我们展示了与代谢和信号通路之间的短暂孵育。 Ca2+ 离子载体 A23187[7] 可诱导无菌敲除 (KO) 遗传精子的体外受精能力我们探索了 A23187 的影响至少部分归因于新陈代谢的变化。使用饥饿和救援方案改变精子代谢，我们观察到细胞内 Ca2+ 此外，我们发现，与 A23187 类似，在缺乏营养物的情况下孵化的精子也会升高。一旦营养物质重新添加到孵化介质中，精子的活力就会得到恢复，这些精子就会失去活力。出乎意料的是，鸡蛋的过度激活率和体外受精（IVF）率更高。在代谢增强的条件下孵化的精子受精能更有效地产生囊胚当这些囊胚转移到该提案具有基本和应用目标，其基本科学目标是。了解这些方法的分子基础，特别强调钙之间的串扰在翻译水平上，我们的目标是使用新的精子孵化条件。提高艺术水平。