Male Contraception Research Center Grant

描述(申请人提供)：世界人口继续以惊人的速度增长，特别是在发展中国家。即使按照每名妇女2.5个孩子的非常乐观的预测，到2100年，全球人口也将增长到150亿以上。此外，约四分之一的怀孕是意外怀孕，导致数百万人堕胎(美国每年有150万例外科或内科堕胎)，全世界每年约有10万名原本健康的年轻妇女死于堕胎并发症。众所周知，男性将使用避孕药(目前美国约30%的避孕方法是通过男性方法完成的)，现有女性方法的安全性和可接受性存在重大问题。因此，开发新型、有效、安全、可逆的男性避孕药是一个极其重要的社会目标。 这项申请中提出的工作旨在增加我们对男性生殖过程的基础和临床知识，特别是与避孕相关的知识。我们有五个研究项目：1)口服睾酮用于男性激素避孕(J.Amory，P.I.)，2)精原干细胞的自我更新和分化(R.Braun，P.I.)，3)环核苷酸磷酸二酯酶对睾丸和精子功能的调节(J.Beavo，P.I.)，4)维甲酸，Stra8，以及精原细胞成熟和睾丸功能的关键因素(M.Griswold，P.I.)以及5)男性激素避孕药的前列腺和心血管效应(W.Bremner博士，P.I.)。我们还提出了一个男性避孕研究员和新调查人员的计划和一个管理核心单位。我们的应用程序将具有不同背景和专业培训的优秀研究人员的人才纳入生殖生物学的互动研究计划。我们组建了这个中心，将精湛的科学与尽可能快地将新的基础知识应用于人类研究的实际目标相结合。我们希望，通过这种方式，我们的工作将满足社会的迫切需要。

DESCRIPTION (provided by applicant): World population continues to increase at a frightening rate, particularly in developing countries. Even at the very optimistic projection of 2.5 children per woman, global population will grow to over 15 billion by year 2100. In addition, approximately one-quarter of all pregnancies are unwanted, leading to millions of abortions (1.5 million surgical or medical abortions annually in the United States) and approximately 100,000 deaths worldwide per year of otherwise healthy young women due to the complications of abortion. It is well established that men will use contraceptives (approximately 30% of all contraception in the U.S. now is accomplished with male methods) and there are substantial problems with the safety and acceptability of existing female methods. Therefore, the development of new, effective, safe, reversible male contraceptives is an extremely important societal goal. The work proposed in this application is designed to increase our basic and clinical knowledge of reproductive processes in the male with particular relevance to contraception. We have five research projects: 1) oral testosterone for male hormonal contraception (Dr. J. Amory, P.I.), 2) spermatogonial stem cell self-renewal and differentiation (Dr. R. Braun, P.I.), 3) regulation of testis and sperm functions by cyclic nucleotide phosphodiesterases (Dr. J. Beavo, P.I.), 4) retinoic acid, Stra8, and key factors in the maturation of spermatogonia and the function of the testis (Dr. M. Griswold, P.I.) and 5) prostate and cardiovascular effects of male hormonal contraceptive regimens (Dr. W. Bremner, P.I.). We also propose a Program for Fellows and New Investigators in Male Contraception and an Administration Core Unit. Our application incorporates the talents of outstanding investigators of varied backgrounds and professional training into an interactive research program in reproductive biology. We have structured this Center to meld superb science with the practical goal of applying new basic knowledge as quickly as possible to studies in human beings. We hope that, in this way, our work will address critical needs of society.