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.

项目摘要不育和不育是影响全球约9％的夫妇的关键健康问题。自第一个成功的“试管”婴儿在1978年使用辅助生殖技术出生了500万以上的婴儿（艺术）。艺术包括体外受精（IVF），introstrine insemination（IUI）等技术，胞质内精子注射（ICSI）和胚胎转移技术。艺术用于人类和经济相关的动物。仅在人类中，IVF和ICSI每年使用约800,000次。总的来说物种，成功怀孕的限制因素是获得优质的植入术对植入和妊娠率有直接影响的胚胎。电容涉及串扰在代谢和信号通路之间。在上一个时期，我们证明了与 Ca2+离子载体A23187 [7]可以从无菌敲除（KO）遗传的精子中诱导体外施肥能力型号。我们假设，至少在某种程度上，A23187的影响是由于代谢的变化所致。什么时候使用饥饿和救援方案改变了精子代谢，我们观察到细胞内Ca2+是高架。此外，我们发现，与A23187相似，在没有营养的情况下孵育的精子变成免疫力。一旦将营养成分添加到孵化培养基中，就可以救出精子运动和那些精子描述了较高的过度活化和增强体外受精（IVF）率的百分比。出乎意料的是，鸡蛋在代谢增强条件下孵育的精子受精于产生胚泡的效率更高这些胚泡产生了更多的植入部位，并在转移到伪怀孕的女性。该建议具有基本和应用的目标。基础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和代谢途径。在翻译层面，我们的目标是使用新颖的精子孵育条件改善艺术。