OHSU

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 the growth and 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 ovarian tissues and cells 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 & Developmental 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. 2013. Structure, function and regulation of the corpus luteum (2013). In: Physiology of Reproduction, 4th ed., J.D. Neill (editor) Elsevier, in press.

Xu J, Xu M, Bernuci MP, Fisher TE, Shea LD, Woodruff TK, Zelinski MB, Stouffer RL. (2013). Primate follicular development and oocyte maturation in vitro. In: Kim S (eds.), Oocyte Biology in Fertility Preservation, New York: Springer Science+Business Media, in press.

Adam M, Saller S. Strobl S, Hennebold JD, Dissen GA, Ojeda SR, Stouffer RL, Berg D, Berg U, Mayerhofer A. (2012).  Decorin is a part of the ovarian extracellular matrix in primates and may act as a signaling molecule. Hum Reprod, 27:3249-58. PMC3472619

McGee WK, Bishop CV, Bahar A, Pohl CR, Chang RJ, Marshall JC, Pau FK, Stouffer RL, Cameron JL. (2012). Elevated androgens during puberty in female rhesus monkeys lead to increased neuronal drive to the reproductive axis: a possible component of polycystic ovary syndrome. Hum Reprod, 27:531-40. PMC3258033

Bishop CV, Satterwhite S, Xu L, Hennebold JD, Stouffer RL. (2012). Microarray analysis of the primate luteal transcriptome during chorionic gonadotrophin administration simulating early pregnancy. Mol Hum Reprod, 18:216-27. PMC3350325

Peluffo MC, Hennebold JD, Stouffer RL, Zelinski MB. (2013). Oocyte maturation and in vitro hormone production in small antral follicles (SAFs) isolated from rhesus monkeys. J Assist Reprod Genet, 30:353-9. PMC3607688

Dancet EA, Brannstrom M, Brasky K, Chai D, Chan AW, Conn PM, Else J, Falconer H, Fazleabas AT, Farah IO, Goddeeris BM, Golos TG, Hau J, Hearn JP, Kariuki TM, Kyama CM, Lebovic DI, Mwenda JM, Ndung'u J, Nyachieo A, Parker J, Slayden OD, Stouffer RL, Strauss JF, Taylor HS, Vanderpoel S, Westergaard JG, Zelinski M, and D'Hooghe TM (2013). The role of scientists and clinicians in raising public support for animal research in reproductive biology and medicine. Biol Reprod 88:33. PMID: 23255340

Tachibana M, Amato P, Sparman M, Gutierrez NM, Tippner-Hedges R, Ma H, Kang E, Fulati A, Lee HS, Sritanaudomchai H, Masterson K, Larson J, Eaton D, Sadler-Fredd K, Battaglia D, Lee D, Wu D, Jensen J, Patton P, Gokhale S, Stouffer RL, Wolf D, and Mitalipov S. (2013). Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer. Cell 153:1228-38. PMC3772789

Waimey KE, Duncan FE, Su HI, Smith K, Wallach H, Jona K, Coutifaris C, Gracia CR, Shea LD, Brannigan RE, Chang RJ, Zelinski MB, Stouffer RL, Taylor RL, and Woodruff TK. (2013). Future Directions in Oncofertility and Fertility Preservation: A Report from the 2011 Oncofertility Consortium Conference. J Adolesc Young Adult Oncol. 2:25-30. PMC3604786

Xu J, Lawson MS, Yeoman RR, Molskness TA, Ting AY, Stouffer RL, and Zelinski MB. (2013). Fibrin promotes development and function of macaque primary follicles during encapsulated three-dimensional culture. Hum Reprod. [Epub ahead of print] PMID: 23608357

 

See a full listing of Dr. Stouffer's publications