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）：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，并作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，实验室小鼠的传统品系在生殖性状的变异程度上是有限的。相比之下，实验室小鼠的近亲，鹿鼠属中的鹿鼠，在生殖解剖，精子生产，形态和运动能力方面表现出物种间的显着差异。这种变异是由于该属内交配系统的极端分化所致。在雌性在一个繁殖季节多次交配的物种中，不同雄性的射精之间存在激烈的竞争，以使她的卵子受精。因此， 在滥交物种中，雄性生殖性状的选择压力很大，可以提高受精成功率;然而，在近缘的一夫一妻制物种中，选择是放松的。因此，Peromyscus的繁殖性状的多样性，使他们成为一个有价值的模型，旨在了解雄性育性的遗传基础的研究，但除此之外，他们也提供了一个全新的视角配子相互作用。当精子从这些小鼠体内释放出来时，它们形成了合作单位--在雌性生殖道内，多个细胞形成了群体，这使得它们能够以比单个精子更大的活力游动。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与它们组合;事实上，这种细胞识别形式如此精细，以至于来自一个雄性的精子甚至可以区分来自同窝出生的同胞的精子。相反，来自一夫一妻制物种的精子不加选择地聚集在一起。该研究旨在利用雄性生殖性状的自然变异以及Peromyscus精子独特的细胞识别和聚集行为，以揭示有助于受精成功的基因。该项目指导阶段的主要目标是确定遗传区域，并最终确定影响精子形态特征的基因，该形态特征与运动力和生殖成功相关，使用遗传作图方法结合代表精子发生不同阶段的睾丸组织的基因表达研究。在该项目的独立阶段，重点将是探索精子聚集行为，以了解群体如何使用综合电子显微镜形成以及为什么他们这样做-通过询问女性生殖道内和复杂环境中合作精子迁移的影响是什么？最后，在了解精子聚集的物理机制后，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精子中细胞识别、识别和粘附的分子机制。总之，这项工作将揭示与男性生育力相关的性状的遗传基础，并提供一个独特的视角配子识别和粘附。 公共卫生关系：了解男性生殖特征的遗传基础将为不孕症和生育力低下提供重要的见解，这是一对夫妇中有一对遇到的问题。此外，仔细的机械，生理和分子特性的选择性精子粘附使用一种新的方法将告知我们的理解配子识别，粘附和通信。这项工作的重点是在一个新兴的啮齿类动物模型，Peromyscus小鼠，这增加了一个新的视角，生育力研究通常在实验室小鼠，不显示极端的自然表型变异或选择性粘附，Peromyscus精子做，或在人类中，这样的对照实验是不可能的。