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. The focus of our work is on the biochemical, hormonal and genetic control of mammalian spermatogenesis, including applied studies in normal men, with the goal of developing new, clinically approved contraceptives for men throughout the world. We have four research projects: 1) Novel ALDH1a2 Inhibitors for Male Contraception (Dr. J. Amory, P.I.);2) Retinaldehyde Dehydrogenases as Male Contraceptive Targets (Dr. M. Griswold, P.I.);3) Spermatogonial Stem Cell Self-Renewal and Differentiation (Dr. R. Braun, P.I.);and 4) Effects of Male Hormonal Contraceptives on Risk Factors for Cardiovascular Disease (Dr. S. Page, P.I.). We also propose an Administration Core Unit, which includes a Program for Fellows and New Investigators. Our proposal 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.

Public Health Relevance

World population continues to increase at a frightening rate, particularly in developing countries, and is predicted to double over the next several decades. One-quarter of all pregnancies are unwanted, resulting in millions of births of unwanted babies, unsafe abortions and maternal deaths. With the known willingness of men to use contraceptives and substantial problems with existing female methods, the development of new, effective, safe, reversible male contraceptives is an extremely important societal goal. Our coordinated, multidisciplinary research program is designed to focus the best science on achieving it.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD042454-12
Application #
8546433
Study Section
Special Emphasis Panel (ZHD1-DRG-H (53))
Program Officer
Lee, Min S
Project Start
2002-09-11
Project End
2017-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
12
Fiscal Year
2013
Total Cost
$1,729,279
Indirect Cost
$329,030
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Cooper, Lori A; Page, Stephanie T (2014) Androgens and prostate disease. Asian J Androl 16:248-55
Surampudi, P; Page, S T; Swerdloff, R S et al. (2014) Single, escalating dose pharmacokinetics, safety and food effects of a new oral androgen dimethandrolone undecanoate in man: a prototype oral male hormonal contraceptive. Andrology 2:579-87
Chao, Jing; Page, Stephanie T; Anderson, Richard A (2014) Male contraception. Best Pract Res Clin Obstet Gynaecol 28:845-57
Amory, John K; Hong, SungWoo; Yu, Xiaozhong et al. (2014) Melphalan, alone or conjugated to an FSH-? peptide, kills murine testicular cells in vitro and transiently suppresses murine spermatogenesis in vivo. Theriogenology 82:152-9
Chakraborty, Papia; Buaas, F William; Sharma, Manju et al. (2014) LIN28A marks the spermatogonial progenitor population and regulates its cyclic expansion. Stem Cells 32:860-73
Amory, John K; Arnold, Samuel; Lardone, MarĂ­a C et al. (2014) Levels of the retinoic acid synthesizing enzyme aldehyde dehydrogenase-1A2 are lower in testicular tissue from men with infertility. Fertil Steril 101:960-6
Paik, Jisun; Haenisch, Michael; Muller, Charles H et al. (2014) Inhibition of retinoic acid biosynthesis by the bisdichloroacetyldiamine WIN 18,446 markedly suppresses spermatogenesis and alters retinoid metabolism in mice. J Biol Chem 289:15104-17
Roth, Mara Y; Shih, Grace; Ilani, Niloufar et al. (2014) Acceptability of a transdermal gel-based male hormonal contraceptive in a randomized controlled trial. Contraception 90:407-12
Anawalt, Bradley D (2013) Approach to male infertility and induction of spermatogenesis. J Clin Endocrinol Metab 98:3532-42
Roth, M Y; Nya-Ngatchou, J J S; Lin, K et al. (2013) Androgen synthesis in the gonadotropin-suppressed human testes can be markedly suppressed by ketoconazole. J Clin Endocrinol Metab 98:1198-206

Showing the most recent 10 out of 73 publications