Siglecs in the Porcine Oviduct: Roles in the Sperm Reservoir and Sperm Immune Response

猪输卵管中的 Siglecs：在精子库和精子免疫反应中的作用

基本信息

批准号：
10607761
负责人：
Leonardo Molina
金额：
$ 4.28万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-02-26 至 2026-03-25
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10607761
关键词：
Address Adhesions Affinity Binding Biochemical Biological Biological Assay Cell Line Cells Chemotaxis Complex Contraceptive methods Data Deposition Development Diagnosis Educational workshop Embryonic Development Environment Epithelial Cells Epithelium Faculty Family suidae Female Fertility Fertilization Gene Expression Genomic approach Germ Cells Glycobiology Glycoconjugates Glycolipids Goals Grant Hamsters Hour Illinois Immune Immune response Immune system Immunohistochemistry Immunology Immunosuppression In Vitro Infiltration Innate Immune Response Insemination Knock-out Knowledge Learning Lectin Leucocytic infiltrate Leukocyte Chemotaxis Ligands Location Longevity Mammalian Oviducts Mammals Mass Spectrum Analysis Measures Mediating Mediator Mentors Migration Assay Modeling Molecular Neuraminidase Organ Outcome Phagocytes Polysaccharides Proteins Rattus Regulation Reproduction Reproductive Biology Research Research Training Resources Role Science Scientist Sialic Acids Site Structure Surface System Techniques Testing Tissues Training Tube Universities Uterus Writing career career development cell type contraceptive target data management experience experimental study gamete transport idiopathic infertility immunoregulation in vivo in vivo Model innovation insight interdisciplinary approach male novel novel strategies practical application prevent professor programs receptor reproductive tract response responsible research conduct senior faculty sialic acid binding Ig-like lectin sialoadhesin sialylation sperm cell success sugar transcription factor transcriptome sequencing

项目摘要

Project Summary/Abstract Siglecs in the Porcine Oviduct: Roles in the Formation of the Sperm Reservoir and Sperm Immune Response In mammals, only a small fraction of the deposited spermatozoa in the female reproductive tract reach the oviduct. Once in the oviduct, sperm bind to the oviductal epithelium, forming the functional sperm reservoir, which is crucial in prolonging sperm lifespan by inducing sperm into a quiescent state and providing these foreign gametes with an immune-suppressed environment. Siglecs are immunomodulatory receptors that recognize sialic acid-containing glycoconjugates. Using the pig as a model, we have discovered the presence of up to eight different Siglecs in the porcine oviduct, five of which are immune inhibitory. We have also characterized the N- and O-glycans and glycolipids present in porcine spermatozoa. Our results have identified the presence of several sialic acid-containing glycoconjugates on porcine sperm that are ligands for Siglecs. We hypothesize that the interactions of sialylated glycans of sperm with Siglecs from the oviduct are essential for sperm adhesion to the epithelium and sperm survival by suppressing leukocyte infiltration and the local innate immune response. The overall goal of this study is to develop a clear understanding of the role of Siglecs in the oviduct and sperm sialic acids during the formation of the sperm reservoir. The Specific Aims are 1) to determine the cellular location and abundance of Siglecs in the oviduct epithelium and sialic acid terminating glycans on sperm, 2) to determine the role of Siglec-1 and other Siglecs in sperm adhesion to oviduct cells, and 3) to determine the role of oviduct Siglecs in local immune regulation upon sperm-oviduct interactions. To address these aims I will utilize a combination of biochemical, cell and molecular, biological, and genomic approaches along with both in-vitro and in-vivo models. The findings from this study have practical applications such as enhanced diagnosis of idiopathic infertility and the development of novel approaches to regulating fertility such as the discovery of new contraceptive targets. This research training plan will provide me with training in a variety of cutting-edge and foundational techniques using an interdisciplinary approach that includes reproduction, immunology, and glycobiology. Moreover, it will support opportunities for career development to prepare me for a successful career in science. The outstanding scientific environment of the University of Illinois will provide me with multiple learning opportunities and the resources to accomplish this study. Dr. Miller, with proven mentoring experience and expertise in the study of the sperm-oviduct interaction, as well as my co-sponsors Dr. McKim and Dr. Nowak, will guide me in the success of the proposed research training plan and my scientific career development.

项目概要/摘要猪输卵管中的 Siglecs：在精子库形成和精子免疫中的作用回复在哺乳动物中，只有一小部分沉积在雌性生殖道中的精子到达输卵管。一旦进入输卵管，精子就会与输卵管上皮结合，形成功能性精子库，通过诱导精子进入静止状态并提供这些，对于延长精子寿命至关重要具有免疫抑制环境的外来配子。 Siglecs 是免疫调节受体识别含唾液酸的糖复合物。以猪为模型，我们发现了存在猪输卵管中含有多达八种不同的 Siglec，其中五种具有免疫抑制作用。我们还有表征了猪精子中存在的 N-和 O-聚糖和糖脂。我们的结果已确定猪精子上存在几种含唾液酸的糖复合物，它们是 Siglecs 的配体。我们假设精子的唾液酸化聚糖与来自输卵管的 Siglecs 的相互作用至关重要通过抑制白细胞浸润和局部白细胞浸润来促进精子粘附到上皮和精子存活先天免疫反应。本研究的总体目标是清楚地了解在精子储存库形成过程中，输卵管中的 Siglecs 和精子唾液酸。具体目标是 1) 确定Siglecs在输卵管上皮和唾液酸中的细胞位置和丰度终止精子上的聚糖，2) 确定 Siglec-1 和其他 Siglec 在精子粘附中的作用输卵管细胞，3) 确定输卵管 Siglecs 在精子-输卵管局部免疫调节中的作用互动。为了实现这些目标，我将结合生物化学、细胞和分子、生物、和基因组方法以及体外和体内模型。这项研究的结果实际应用，例如特发性不孕症的增强诊断和新型药物的开发调节生育能力的方法，例如发现新的避孕目标。这个研究训练计划将为我提供各种前沿和基础的训练使用跨学科方法的技术，包括生殖、免疫学和糖生物学。此外，它将支持职业发展机会，为我在科学领域的成功职业生涯做好准备。伊利诺伊大学优秀的科研环境将为我提供多元的学习机会完成这项研究的机会和资源。米勒博士拥有丰富的指导经验和在精子与输卵管相互作用研究方面的专业知识，以及我的共同发起人 McKim 博士和 Nowak 博士，将指导我所提议的研究培训计划的成功和我的科学职业发展。