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: 8442021
• 负责人: Heidi S Fisher
• 金额: $ 12.97万
• 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 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8442021
• 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）：有助于实验室小鼠生殖成功的基因为哺乳动物生殖的分子、发育和生理过程提供了重要的见解，并已成为人类不育研究的模型。然而，与自然界中观察到的变异程度相比，传统实验室小鼠品系的繁殖性状变异程度有限。相比之下，与实验室小鼠关系密切的白鼠属鹿鼠，在不同物种的生殖解剖结构、精子产生、形态和运动能力方面表现出显着差异。这种变异是由于属内交配系统的极端分歧造成的。在雌性在繁殖季节多次交配的物种中，不同雄性的射精之间会为了卵子的受精而进行激烈的竞争。据此，有 对雄性生殖性状产生强大的选择压力，从而提高杂乱物种的受精成功率；然而，在密切相关的一夫一妻制物种中，选择是宽松的。因此，白鼠繁殖性状的多样性使它们成为旨在了解雄性生育力遗传基础的研究的有价值的模型，但此外，它们还为配子相互作用提供了全新的视角。当精子从这些小鼠体内释放出来时，它们会形成合作单位——多个细胞在雌性生殖道内形成群体，这使得它们比单个精子能够以更大的活力游动。至少在一种物种中，即精子竞争最激烈的物种中，精子能够识别最相关的细胞并选择性地与它们分组；事实上，这种形式的细胞识别非常精细，以至于雄性的精子甚至可以区分同窝同窝兄弟姐妹的精子。相比之下，来自一夫一妻制物种的精子不加区别地群体。这项研究旨在利用雄性生殖特征的自然变异以及白鼠精子独特的细胞识别和聚集行为来揭示有助于受精成功的基因。该项目指导阶段的主要目标是利用基因图谱结合代表不同阶段的睾丸组织的基因表达研究，确定遗传区域和最终影响精子形态特征的基因，该形态特征与活力和生殖成功相关。的精子发生。在该项目的独立阶段，重点将是探索精子聚集行为，以了解如何使用综合电子显微镜形成群体以及它们这样做的原因 - 通过询问女性生殖道内和复杂环境中精子合作迁移的影响是什么？最后，在了解精子聚集所涉及的物理机制的基础上，本研究将应用在指导阶段实施的类似遗传和基因组技术来揭示精子聚集体大小的遗传基础以及参与细胞识别、区分和粘附的分子机制。精子。总的来说，这项工作将为与男性生育力相关的性状的遗传基础提供新的线索，并为配子识别和粘附提供独特的视角。 公共卫生相关性：了解男性生殖特征的遗传基础将为了解不孕症和生育力低下（一对夫妻都会遇到的问题）提供重要见解。此外，使用新方法对选择性精子粘附进行仔细的机械、生理和分子表征将有助于我们理解配子识别、粘附和交流。这项工作重点关注一种新兴啮齿动物模型——白腹鼠小鼠的自然可变表型，这为通常在实验室小鼠中进行的生育力研究增加了新的视角，实验室小鼠没有表现出白腹鼠精子或人类所表现出的极端自然表型变异或选择性粘附。 ，这样的受控实验是不可能的。