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. Molecular and cellular approaches are being applied to identify genes and their products that are essential for ovulation of the follicle, conversion of the follicle into the corpus luteum, and extension of luteal structure-function into early pregnancy. In vitro and in vivo (animal) experiments are testing which genes are regulated by hormones or local factors, and if gene products or pharmaceutical antagonists have potential of novel contraceptive agents for women.

Stouffer’s group is also working with a consortium of scientists from OHSU, University of Pittsburgh and University of California, Los Angeles, to investigate the effects of chronic androgen exposure with or without a typical western-style (high fat) diet, on reproduction and metabolism of young adult, female monkeys. The goal is to determine if these experimental manipulations result in changes reminiscent of those seen in adolescent girls at risk for polycystic ovarian syndrome, and hence provide insight into the causes and possible treatment of this common infertility disorder in women.

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 former Chief 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 18 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, RL, and Hennebold, JD. (In Press 2013) Structure, Function and Regulation of the Corpus Luteum. In Knobil and Neill's Physiology of Reproduction (Plant, T. M., and Zeleznik, A., eds),  pp. 475-526.

Peluffo, MC, Stanley, J, Braeuer, N, Rotgeri, A, Fritzemeier, KH, Fuhrmann, U, Buchmann, B, Adevai, T, Murphy, MJ, Zelinski, MB, Lindenthal, B, Hennebold, JD, and Stouffer, RL. (2014) A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaques. Hum Reprod 10.1093/humrep/deu083. PMID: 24781425. PMC in process

Rodrigues, J, Xu, J, Marinho, R, Caetano, J, Zelinski, M, Stouffer, R, and Navarro, P (2014). In vitro follicle maturation (IFM): potential for fertility preservation in patients with cancer. Journal of Assisted Reproduction and Genetics Submitted. PMID., PMC in process

Stouffer, RL, Bishop, CV, Bogan, RL, Xu, F, and Hennebold, JD. (2013). Endocrine and local control of the primate corpus luteum. Reprod Biol 13, 259-271. PMID: 24287034. PMC in process

Bishop, CV, Aazzerah, RA, Quennoz, LM, Hennebold, JD, and Stouffer, RL. (2014). Effects of steroid ablation and progestin replacement on the transcriptome of the primate corpus luteum during simulated early pregnancy. Mol Hum Reprod 20, 222-234. PMC3925330

Fisher, TE, Molskness, TA, Villeda, A, Zelinski, MB, Stouffer, RL, and Xu, J. (2013) Vascular endothelial growth factor and angiopoietin production by primate follicles during culture is a function of growth rate, gonadotrophin exposure and oxygen milieu. Hum Reprod 28, 3263-3270. PMC3829578

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, Adv Exp Med Biol, 761:43-67. PMC4007769

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

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

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 28:2187-200. PMC3712659

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

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

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


 

See a full listing of Dr. Stouffer's publications