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

项目摘要/摘要 猪输卵管中的Siglecs：在精子库形成和精子免疫中的作用 响应 在哺乳动物中，只有一小部分沉积在雌性生殖道的精子可以到达 输卵管。一旦进入输卵管，精子就与输卵管上皮结合，形成有功能的精子储存库， 这在通过诱导精子进入静止状态并提供这些 具有免疫抑制环境的外来配子。Siglecs是免疫调节受体， 识别含唾液酸的糖共轭化合物。以猪为模型，我们发现了 猪输卵管中多达八种不同的Siglecs，其中五种具有免疫抑制作用。我们还有 描述了猪精子中存在的N-和O-糖聚糖和糖脂的特征。我们的研究结果表明 猪精子上存在几种含唾液酸的糖偶联物，它们是Siglecs的配体。 我们推测精子唾液酸化的糖链与输卵管中的Siglecs之间的相互作用是必不可少的。 通过抑制白细胞浸润和局部抑制精子与上皮细胞的黏附和精子存活 先天免疫反应。这项研究的总体目标是对 精子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 终止精子上的糖链，2)确定Siglec-1和其他Siglecs在精子黏附中的作用 输卵管细胞，以及3)输卵管Siglecs在精子-输卵管局部免疫调节中的作用 互动。为了达到这些目标，我将利用生物化学、细胞和分子、生物学、 以及基因组方法以及体外和体内模型。这项研究的发现有 特发性不孕症的增强诊断和新型药物的开发等实际应用 调节生育率的方法，如发现新的避孕目标。 这项研究培训计划将为我提供各种前沿和基础性的培训 使用包括生殖、免疫学和糖生物学在内的跨学科方法的技术。 此外，它还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。 伊利诺伊大学卓越的科学环境将为我提供多重学习 完成这项研究的机会和资源。米勒博士，拥有成熟的指导经验和 在精子-输卵管相互作用研究方面的专业知识，以及我的共同赞助人麦克金博士和诺瓦克博士， 将指导我成功地完成拟议的研究培训计划，并指导我的科学职业发展。

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.