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 #
2U54HD042454-11
Application #
8390987
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
2012-09-17
Budget End
2013-06-30
Support Year
11
Fiscal Year
2012
Total Cost
$1,735,404
Indirect Cost
$578,108
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Berkseth, Kathryn E; Rubinow, Katya B; Melhorn, Susan J et al. (2018) Hypothalamic Gliosis by MRI and Visceral Fat Mass Negatively Correlate with Plasma Testosterone Concentrations in Healthy Men. Obesity (Silver Spring) 26:1898-1904
Rubinow, Katya B; Houston, Barbara; Wang, Shari et al. (2018) Androgen receptor deficiency in monocytes/macrophages does not alter adiposity or glucose homeostasis in male mice. Asian J Androl 20:276-283
Chen, Yan; Zhu, Jin-Yi; Hong, Kwon Ho et al. (2018) Structural Basis of ALDH1A2 Inhibition by Irreversible and Reversible Small Molecule Inhibitors. ACS Chem Biol 13:582-590
Paik, Jisun; Treuting, Piper M; Haenisch, Michael et al. (2018) Can inhibition of retinoic acid biosynthesis function as a non-hormonal female contraceptive? Contraception :
Sharma, Manju; Braun, Robert E (2018) Cyclical expression of GDNF is required for spermatogonial stem cell homeostasis. Development 145:
Rubinow, Katya B; Vaisar, Tomas; Chao, Jing H et al. (2018) Sex steroids mediate discrete effects on HDL cholesterol efflux capacity and particle concentration in healthy men. J Clin Lipidol 12:1072-1082
Haenisch, Michael; Treuting, Piper M; Brabb, Thea et al. (2018) Pharmacological inhibition of ALDH1A enzymes suppresses weight gain in a mouse model of diet-induced obesity. Obes Res Clin Pract 12:93-101
Swerdloff, Ronald S; Dudley, Robert E; Page, Stephanie T et al. (2017) Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels. Endocr Rev 38:220-254
Ayoub, R; Page, S T; Swerdloff, R S et al. (2017) Comparison of the single dose pharmacokinetics, pharmacodynamics, and safety of two novel oral formulations of dimethandrolone undecanoate (DMAU): a potential oral, male contraceptive. Andrology 5:278-285
Rubinow, Katya B; Chao, Jing H; Hagman, Derek et al. (2017) Circulating sex steroids coregulate adipose tissue immune cell populations in healthy men. Am J Physiol Endocrinol Metab 313:E528-E539

Showing the most recent 10 out of 129 publications