Richard L. Stouffer

A major unanswered question in reproductive research is which factors control the cyclic activity of the ovary. The female ovarian or menstrual cycle lasts 28 days. In the first half of the cycle, one follicle is selected to mature and release an egg for possible fertilization in the reproductive tract; in the second half, the follicle wall is converted into the corpus luteum - an endocrine gland that secretes the hormone progesterone that is vital for the initiation and maintenance of pregnancy.

Richard Stouffer and his associates investigate the factors controlling ovulation of the mature follicle at midcycle, as well as development of the corpus luteum from the ovulatory follicle and its function until the end of the menstrual cycle or into early pregnancy. Studies on intact monkeys and research on isolated cells or cell components are unraveling the complex interaction between substances produced within the ovary (e.g., progesterone and angiogenic factors) and those coming from other organs (gonadotropins from the pituitary gland and placenta) in controlling the ovulatory follicle and corpus luteum.

Stouffer's discovery that progesterone-producing cells within the ovulatory follicle and corpus luteum also contain progesterone receptors led to research identifying an essential role for this steroid hormone within the ovary for follicle rupture and release of the egg, and for development of the corpus luteum. Additional studies are identifying the angiogenic factors (e.g., vascular endothelial growth factor, angiopoietin) that promote the unique development of blood vessels in the adult ovary during the menstrual cycle, and whether aberrant production of these factors is a cause of infertility disorders or side effects during assisted reproductive protocols. These investigations led to ongoing studies in collaboration with other researchers to evaluate the potential of antiprogestins, antiangiogenic agents and inhibitors of oocyte maturation or ovulation as contraceptives in preclinical trials on nonhuman primates.

Stouffer's group is also working with the Assisted Reproductive Technologies (ART) Laboratory and a multi-center Oncofertility Consortium to elucidate the hormonal and local factors critical for normal, timely development of the primate ovarian follicle and its enclosed egg.

This research is directly relevant to continued efforts to improve the clinical approaches to treating infertility and high-risk pregnancy, and to develop new methods of contraception. New information will also aid in the preservation of nonhuman primates through assisted reproductive techniques, such as in vitro fertilization.

Biography

Richard Stouffer is Senior Scientist and Head of the Division of Reproductive Sciences, and Professor of Obstetrics & Gynecology, and Physiology & Pharmacology in the OHSU School of Medicine. He is ONPRC director of the NIH-sponsored Specialized Cooperative Center Program for Infertility and Reproduction Research at OHSU, which is part of a network of 14 centers in the United States. He is also co-director of the NIH-sponsored Contraceptive Development Research Center at OHSU, which networks with 3 other centers in the U.S.A. He earned a Ph.D. in physiology/pharmacology from Duke University Medical School in 1975. After two years as a staff research fellow in the Reproductive Research Branch, National Institute of Child Health and Human Development, Dr. Stouffer became an Assistant Professor of Physiology at the University of Arizona Health Sciences Center, where he remained until his 1985 appointment at ONPRC, OHSU.

Key Publications

Stouffer, R.L. 2006. Structure, function and regulation of the corpus luteum. In: Physiology of Reproduction, 3rd ed., J.D. Neill (editor) Elsevier.

Peluffo MC, Young KA, Hennebold JD, Stouffer RL. Expression and regulation of tumor necrosis factor (TNF) and TNF-receptor family members in the macaque corpus luteum during the menstrual cycle. Mol Reprod Dev, 76:367-378, 2008. PMID 18932199

Bishop CV, Hennebold JD, Stouffer RL. The effects of luteinizing hormone ablation/replacement versus steroid ablation/replacement on gene expression in the primate corpus luteum. Molec Hum Reprod 15:181-193, 2009. PMID 19168862

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