The evolutionary and molecular mechanisms underlying sperm performance in an emer

精子在早期表现的进化和分子机制

• 批准号: 8734268
• 负责人: Heidi S Fisher
• 金额: $ 13.02万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8734268
• 关键词: Address; Adhesions; Anatomy; Behavior; Bioinformatics; Breeding; Candidate Disease Gene; Cells; Chromosome Mapping; Communication; Complement; Complex; Contraceptive methods; Couples; DNA; Data; Deer Mouse; Development; Developmental Process; Discrimination; Electron Microscopy; Employee Strikes; Environment; Evolution; Exhibits; Female; Fertility; Fertility Study; Fertilization; Functional disorder; Funding; Gene Expression; Gene Expression Profile; Genes; Genetic; Genome; Genomics; Germ Cells; Goals; Human; In Situ; In Vitro; Individual; Infertility; Knowledge; Laboratory mice; Learning; Life; Light; Male Infertility; Maps; Mechanics; Mentors; Methodology; Microscopy; Modeling; Molecular; Morphology; Mouse Strains; Movement; Mus; National Research Service Awards; Nature; Partner in relationship; Performance; Peromyscus; Phase; Phenotype; Physiological; Physiological Processes; Population; Postdoctoral Fellow; Production; Public Health; Quantitative Trait Loci; Relative (related person); Reproduction; Research; Rodent; Rodent Model; Scanning Transmission Electron Microscopy Procedures; Science; Seasons; Shapes; Siblings; Sister; Site; Sperm Midpiece; Sperm Motility; Spermatogenesis; Staging; Structure; Study models; Swimming; System; Techniques; Testicular Tissue; Time; United States National Institutes of Health; Variant; Work; base; career; cell motility; design; egg; genome-wide; genome-wide linkage; improved; innovation; insight; male; migration; molecular size; novel; novel strategies; pressure; programs; reproductive; reproductive success; research study; skills; sperm cell; success; theories; tool; trait; transcriptome sequencing; transcriptomics

DESCRIPTION (provided by applicant): Genes contributing to reproductive success in laboratory mice have provided important insights into the molecular, developmental and physiological processes underlying mammalian reproduction and have served as models for studies of human infertility. Traditional strains of laboratory mice, however, are limited in the degree of variation in reproductive traits compared to the extent of variation observed in nature. In contrast, a close relative to the laboratory mouse, deer mice in the genus Peromyscus, exhibit striking differences in reproductive anatomy, sperm production, morphology and motility among species. This variation is due to the extreme divergence in mating system within the genus. In species in which females mate multiple times over a breeding season, there is intense competition between ejaculates of different males for fertilization of her eggs. Accordingly, there is strong selective pressure on male reproductive traits that improve fertilization success in promiscuous species; in closely-related monogamous species, however, selection is relaxed. Thus, the diversity of reproductive traits in Peromyscus makes them a valuable model for studies aimed at understanding the genetic basis of male fertility but, in addition, they also offe an entirely new perspective on gametic interactions. When sperm are released from these mice they form cooperative units-multiple cells form groups within the female reproductive tract, which enable them to swim with greater motility compared to individual sperm. In at least one species, the species in which sperm competition is most intense, sperm are able to recognize the most related cells and selectively group with them; in fact, this form of cellular recognition s so refined that sperm from one male can even discriminate against sperm from full sibling littermate. In contrast, sperm from a monogamous species group indiscriminately. The proposed study is designed to exploit the natural variation in male reproductive traits as well as the uniqu cellular recognition and aggregation behavior of Peromyscus sperm to reveal the genes that contribute to fertilization success. The primary goal in the mentored phase of this project is to identify genetic regions and ultimately genes influencing a morphological trait of sperm that is associated with motility and reproductive success using a genetic mapping approached combined with gene expression studies of the testicular tissue that represent different stages of spermatogenesis. During the independent phase of this project the focus will be on exploring sperm aggregation behavior to understand both how groups form using integrative electron microscopy and why they do - by asking what is the effect of cooperative sperm migration within the female reproductive tract and in complex environments? Finally, with an understanding of the physical mechanisms involved in sperm aggregation, this study will apply similar genetic and genomic techniques implemented in the mentored phase to reveal the genetic basis of sperm aggregate size and the molecular mechanisms involved in cellular recognition, discrimination and adhesion in sperm. In total, this work will shed new light on the genetic basis of traits associated with male fertility and offer a unique perspective on gametic recognition and adhesion. PUBLIC HEALTH RELAVANCE: Understanding the genetic basis of male reproductive traits will provide important insights into infertility and sub fertility, a problem encountered by 1 in 1 couples. Moreover, a careful mechanical, physiological and molecular characterization of selective sperm adhesion using a novel approach will inform our understanding of gamete recognition, adhesion and communication. This work focuses on naturally variable phenotypes in an emerging rodent model, Peromyscus mice, which adds a new perspective to fertility studies commonly performed in laboratory mice, which do not show the extreme natural phenotypic variation or selective adhesion that Peromyscus sperm do, or in humans, where such controlled experiments are not possible.

描述（由申请人提供）：在实验室小鼠中有助于生殖成功的基因为哺乳动物生殖的基础的分子，发育和生理过程提供了重要的见解，并已成为研究人类不孕症的模型。然而，与自然观察到的变异程度相比，传统的实验室小鼠菌株的生殖特征变化程度受到限制。相比之下，相对于实验室小鼠，peromyscus属的鹿小鼠在物种之间的生殖解剖学，精子产生，形态和运动性上表现出明显的差异。这种变化是由于属内交配系统的极端差异所致。在雌性在一个繁殖季节中多次交配的物种中，不同雄性射精的卵子施肥之间存在激烈的竞争。因此，那里 对男性生殖特征的强烈选择压力，可以改善滥交物种的受精成功。但是，在与一夫一妻紧密相关的物种中，选择放松。因此，peromyscus生殖特征的多样性使它们成为旨在了解男性生育能力的遗传基础的研究的宝贵模型，但此外，它们也对配子相互作用有了全新的观点。当这些小鼠从这些小鼠中释放精子时，它们会形成合作单元 - 多层细胞在女性生殖道中形成组，这使其与单个精子相比，它们能够以更大的运动性游泳。在至少一个物种中，精子竞争最激烈的物种，精子能够识别最相关的细胞并选择性地分组。实际上，这种细胞识别的形式如此精致，以至于一个雄性的精子甚至可以歧视全同窝同伊的精子。相反，来自一夫一妻群的精子不加区别。拟议的研究旨在利用男性生殖特征的自然变异以及peromyscus精子的唯一细胞识别和聚集行为，以揭示有助于受精成功的基因。该项目的指导阶段的主要目标是鉴定遗传区域和最终影响精子形态学特征的基因，该特征与运动映射接近与睾丸组织的基因表达研究相结合，与运动图相关联，并获得了代表不同阶段的基因表达研究精子发生。在该项目的独立阶段，重点将放在探索精子聚集行为上，以了解两组如何使用集成电子显微镜以及它们这样做的原因 - 询问在女性生殖道和复杂环境中合作精子迁移的影响是什么？最后，通过了解精子聚集涉及的物理机制，本研究将应用在指导阶段实施的类似遗传和基因组技术，以揭示精子骨料大小的遗传基础以及与细胞识别，歧视和粘附有关的分子机制的遗传基础精子。总的来说，这项工作将为与男性生育能力相关的特征的遗传基础提供新的启示，并就配子识别和粘附提供独特的观点。 公共卫生救助：了解男性生殖特征的遗传基础将为不育和亚生育能力提供重要的见解，这是1对夫妇遇到的问题。此外，使用新方法对选择性精子粘附的仔细的机械，生理和分子表征将有助于我们对配子识别，粘附和交流的理解。这项工作着重于新兴的啮齿动物模型Peromyscus小鼠中的自然可变表型，这为在实验室小鼠中通常进行的生育研究增添了新的观点，这些研究没有显示出极端的自然表型变异或Peromyscus精子所做的极端自然表型变异，如果无法进行这种受控的实验。