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临床试验/NCT02864329
NCT02864329已完成不适用

Small RNA Pathways in Mammalian Gametogenesis

Weill Medical College of Cornell University1 个研究点 分布在 1 个国家目标入组 182 人开始时间: 2014年4月最近更新:
适应症

试验速览

阶段
不适用
状态
已完成
入组人数
182
试验地点
1
主要终点
Using RNA from men with normal spermatogenesis and men with infertility for multiplexed deep sequencing to identify differentially expressed miRNAs

研究概览

简要总结

Basic and clinical research is revealing that various noncoding and small RNAs play important and diverse roles in germ cell development and quality, including X/Y silencing during meiosis, gene regulation, DNA damage responses, and protection of the genome against transposable elements. Indeed, mammalian germ cells are known to harbor multiple small RNA species, including small interfering RNAs (siRNA), microRNAs (miRNA), and germline- specific PIWI- interacting RNAs (piRNA). However, their mechanistic roles in gametogenesis and human infertility are largely uncharacterized. The goal of this study is to elucidate the role of small RNA pathways in the events that give rise to viable euploid gametes. Four projects and three cores are included in this study.

详细描述

Project 2 (PI: Dr. Darius Paduch): Role of Small RNAs in male infertility. The leading hypothesis of this project is based on extensive preliminary results obtained by this group showing that 70% of miRNA expressed from human testis are highly conserved in humans and rodents. The investigators hypothesize that differentially expressed miRNAs in men with infertility lead to changes in levels of target messenger RNAs (mRNAs) involved in key regulatory pathways in cell biology. The results of this project will lead to better understanding of miRNAs' role in male reproduction and have strong potential to enable the development of new miRNA-based or miRNA-regulating therapies. This project will help to develop new transgenic animals to study miRNA in vivo with implications not only for infertility, but also biology of testicular cancer. Derived RNA based therapies have the potential to be less invasive, less toxic, and more effective in treating these serious and increasingly prevalent conditions.

Core A (PI: Dr. Paula E. Cohen): Administration Core. The main objective of the Administrative Core (Core A) is to provide a structure and support mechanism to the entire Center for Reproductive Genomics (CRG). The Admin core will facilitate interactions across the Ithaca and Manhattan campuses of Cornell University, will encourage research in small RNA biology, both in reproductive medicine and across clinical disciplines, and will promote strong training in reproductive medicine that encourages a translational focus. In general, the Admin core will focus efforts on three major philosophies: translational and innovative research, teaching, and outreach.

Core B (PI: Dr. Andrew Grimson): RNA Sequencing Core. The main objective of the RNA Sequencing Core (RSC) is to provide users with efficient and high quality access to cutting-edge sequencing technologies. These sequencing technologies will be used by all members of this P50-proposal, and made available to other P50-centers. Importantly, all members of this P50 are relying on access to these technologies to achieve their project goals. By centralizing sequencing at the RSC, sequencing will be performed at a lower cost and with greater efficiency that would be possible for individual users.

Core C (PI: Dr. Peter Schlegel): Outreach Core The goals of this outreach core are two-fold: (1) to provide a scientific and technical resource for clinicians interested in embarking on research involving small RNA biology in their physiological system of interest, and (2) to provide outreach to the community by means of a state- of-the-art lecture series. The Innovation Seminars in Reproductive Technologies Series (InSeRT), in order to educate patients about the latest advances in our understanding of the genetic and epigenetic basis for human disease.

研究设计

研究类型
Observational
观察模型
Cohort
时间视角
Retrospective

入排标准

年龄范围
18 Years 至 90 Years(Adult, Older Adult)
性别
Male
接受健康志愿者

入选标准

  • Men between the ages of 18-90 who have testicular cancer and underwent surgery at Weill Cornell Medicine.

排除标准

  • Women, men outside of the age parameters

结局指标

主要结局

Using RNA from men with normal spermatogenesis and men with infertility for multiplexed deep sequencing to identify differentially expressed miRNAs

时间窗: 5 years

Detect target mRNAs through correlation analysis of actual mRNA expression profiles obtained from the same patients. At the end of the proposed funding period, project 2 will have identified and confirmed a set of approximately 20-30 miRNA:mRNA interactions in male infertility.

次要结局

未报告次要终点

研究者

申办方类型
Other
责任方
Sponsor

研究点 (1)

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