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The actions of steroid hormones on oviduct function

类固醇激素对输卵管功能的作用

基本信息

批准号：
10112938
负责人：
Wipawee Joy Winuthayanon
金额：
$ 35.56万
依托单位：
WASHINGTON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-12 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10112938
关键词：
Animals Assisted Reproductive Technology Atlases Automobile Driving Cells Cilia Control Animal Culture Media Data Defect Dependence Disease Embryo Embryo Deaths Embryonic Development Ensure Environment Epigenetic Process Epithelial Epithelial Cells Estrogen Receptor alpha Estrogens Estrus Female Fertility Fertilization Functional disorder Gene Expression Gene Expression Profile Genes Germ Cells Goals Heterogeneity Human Impairment In Vitro Incidence Infertility Knock-out Knowledge Mammalian Oviducts Maps Mediating Metabolic Molecular Morphology Mus Nature Nuclear Receptors Organ Outcome Ovarian Ovarian Steroid Hormone Ovarian hormone Play Population Pre-implantation Embryo Development Pregnancy Pregnancy Rate Prevention Progesterone Protein Secretion Regulation Reproductive Technology Resolution Role Seminal Signal Transduction Sperm Transport Steroids Technology Testing Time Tube Uterine cavity Uterus base blastocyst cell type design fluid flow gamete transport improved in vivo insight migration mouse model novel premature response single-cell RNA sequencing spatiotemporal sperm cell steroid hormone success transcriptome

项目摘要

PROJECT SUMMARY/ABSTRACT Approximately 14% of infertility cases that undergo assisted reproductive technologies (ART) are due to Fallopian tube dysfunction. In 2015 alone, over 230,000 ART cycles were performed in the U.S, yet, less than 30% of those cycles resulted in pregnancy. Moreover, the incidence of epigenetic disorders is increased in in vitro-conceived embryos. A major contributing factor to the poor success and inherent problems associated with ART is our lack of understanding of the nature of the oviductal environment. Attempts to improve culture media by mimicking the oviductal environment, however, have been limited by our lack of understanding of the optimal microenvironment provided by the oviduct and how it changes during the course of preimplantation embryo development. Therefore, our long-term goal is to identify the key factors produced by each epithelial cell type that are crucial for sperm migration, fertilization, embryo development, and embryo transport. It has been established that ovarian-derived steroid hormones, estrogen (E2) and progesterone (P4), modulate the function of epithelial cell lining of the oviduct. However, how steroids modulate the function of these epithelial cell populations that are tailored for each specific stage during pregnancy establishment is undefined. As such, in this study, we will develop a spatiotemporal map of steroid actions and their effect on oviductal epithelial cells during the course of sperm/embryo transport and embryo development. Specifically, using mouse models, we will determine how E2 and P4 mediate distinct populations of epithelial cells of the oviduct to create an appropriate milieu that changes at different points in time during the course of pre-implantation embryo development. Our central hypothesis is that fine-tuning of the oviductal epithelium through the actions of E2 and P4 allows the oviduct to create a malleable environment that supports fertilization and responds to the changing metabolic needs of developing embryos. We propose to: determine the roles of 1) E2 and 2) P4 signals through their classical nuclear receptor either in the secretory or the ciliated epithelial cell of the oviduct during the sperm migration, the time of fertilization, pre-implantation embryo development, and embryo transport. Also, 3) gene expression profile corresponding to E2 and P4 action in epithelial cell populations at different regions of the oviduct and at distinct stages will be defined at a single cell resolution using mouse models. The successful completion of these aims will fill fundamental gaps in knowledge for two main reasons. First, the information will provide novel insight into the molecular mechanisms driving oviductal functions. Second, understanding which cell populations function during each stages of sperm/embryo transport and embryo development will generate much needed information to optimize culture conditions in an ART setting.

项目总结/文摘