Photo of Richard L. Stouffer, Ph.D.

Richard L. Stouffer Ph.D.

  • (503) 346-5442
    • Professor Oregon National Primate Research Center
    • Professor of Obstetrics and Gynecology School of Medicine
    • Professor of Physiology and Pharmacology School of Medicine
    • Professor of Reproductive & Developmental Sciences, Oregon National Primate Research Center

Since his dissertation research in the laboratory of Dr. David Schomberg, Departments of Physiology & Ob-Gyn, at Duke University in the 1970s, Dr. Stouffer’s primary research has focused on understanding the structure, function and regulation of the ovary. Moreover, as a staff fellow with Dr. Gary Hodgen, in the intramural NICHD program at NIH, he began studies using the nonhuman primate (NHP) as a “translational model” for direct application to ovarian function and its disorders in women. For 8 years, Dr. Stouffer was a member of the Department of Physiology, University of Arizona College of Medicine, where he rose to the rank of tenured Associate Professor.  In 1985, he moved to the Oregon National Primate Research Center to take advantage of its exceptional NHP resources and support services, its outstanding faculty studying NHP reproductive biology, plus the opportunity to train graduate students and postgraduate (Ph.D., M.D.) fellows through NIH-supported training grants and fellowship programs in basic science (Physiology & Pharmacology) and clinical (Ob-Gyn, Medicine/Endocrinology) departments at ONPRC’s home institution, the Oregon Health & Sciences University (OHSU). Dr. Stouffer’s primary appointment is Professor in the Division of Reproductive & Developmental Sciences, ONPRC with active joint appointments as Professor, Departments of Ob-Gyn and Physiology & Pharmacology, OHSU.

Dr. Stouffer’s research program utilizes whole animal, cellular and molecular approaches to unravel the mechanisms controlling follicle development, ovulation and the functional lifespan of the corpus luteum during the menstrual cycle and early pregnancy in rhesus macaques. One NIH R01 grant (which has been active for over 30 years at Arizona and Oregon!) focuses on the endocrine and local control of the primate ovulatory follicle and corpus luteum. This project resulted in the landmark discovery (Hibbert et al., PNAS 93:1897-1901, 1996, PMID: 8700855) that progesterone produced by the dominant follicle in response to midcycle gonadotropin surge is required for ovulation and development of the primate corpus luteum. The later feature, which differs from the mouse model, is supported by novel studies detailing the expression of genomic progesterone receptor in macaque (and human) luteal cells, and spurred Dr. Stouffer’s important studies to elucidate the gonadotropin (LH or CG)- and progesterone– responsive genes in the ovulatory follicle, as well as the corpus  luteum as it ages during the menstrual cycle and early pregnancy (e.g., Xu et al., Mol Hum Reprod 17:152-165, 2011, PMID 21036944; Bishop et al., Mol Hum Reprod 16:216-227, 2012, PMID 22072816). These gene (GED) databases are publicly available, and being used for comparative studies of ovarian function by other investigators. Currently, Dr. Stouffer, in collaboration with Dr. Jon Hennebold, is using attenuated adenoviral vectors to deliver siRNAs to PR and PGRMC1 into the macaque periovulatory follicle to elucidate the role(s) of genomic and nongenomic progesterone receptor signaling pathways in ovulation and corpus luteum development in primates.

Such basic studies provided the groundwork for more applied research using NHPs to understand and improve women’s reproductive health. Evaluation of the transcriptome in the periovulatory follicle provided data supporting a project in a Contraceptive Development & Research Center (U54 HD055744), to discover and develop novel, nonhormonal contraceptives that prevent cumulus-oocyte expansion or follicle rupture, and hence egg release and fertility. Several factors are being considered, but one study in collaboration with Bayer Health Care (formerly Schering AG), Berlin, established that a specific antagonist of prostaglandin E2 receptor 2 (EP2) markedly suppressed fertility in female macaques without altering menstrual cyclicity (Peluffo et al., Hum Reprod 29:1400-1412, 2014, PMID 24781425). Also, Dr. Stouffer directed a successful effort to establish a novel Specialized Cooperative Center on Infertility & Reproduction (HD071836) which is evaluating the effects of chronic hyperandrogenemia and western-style diet (WSD), beginning just prior to puberty, on reproductive and metabolic parameters in young adult female macaques. Preliminary studies in collaboration with Drs. Judy Cameron (University of Pittsburgh), John Marshall (University of Virginia) and Jeffrey Chang (University of California, San Diego) suggest that these treatments lead to a neuroendocrine, metabolic and ovarian phenotype reminiscent in part to polycystic ovary syndrome (McGee et al., A, J Physiol Endocrinol Metab 306: E1292-1304, 2014, PMID 24735887). Recent findings identified ovarian and uterine defects, as well as metabolic changes, that were most pronounced in the combined androgen and WSD treatment group (Bishop et al., Hum Reprod 33:128-139, 2018, PMID29190387). Subsequent fertility protocols established that androgen treatment increased the time required to achieve pregnancy, WSD reduced the number of pregnancies, whereas the combination led to pregnancy loss before term (Bishop et al. Hum Reprod 33:694-705, 2018, PMID29401269). Ongoing studies within the NIH-funded infertility (NCTRI) center are testing the hypotheses that (1) many of these defects resulting from hyperandrogenemia and diet-induced metabolic changes will worsen with continued treatment, but (2) are reversible/treatable. 

In addition to a world-renown research program pertaining to women’s reproductive health, as recognized by the Society for the Study of Reproduction (SSR Research Award, 2007) and the American Society for Reproductive Medicine, (ASRM Distinguished Researcher Award, 2010), Dr. Stouffer has broad experience in leadership and mentorship both locally and nationally. He served on the Board of Directors and as President of SSR (1990-1993, 1995-1996), and member then chair of the NIH REN Study Section (1991-1995; 2000-2002). He is director/PI and Co-PI of the NIH-funded Oregon Infertility SCCPIR/NCTRI centers (1999-2018) and the Oregon Contraceptive CDRC center (2007-2018). Importantly, Dr. Stouffer served as chief of the Division of Reproductive & Developmental Sciences from 1996-2014, until stepping down to return to full-time research. He remains active as chair of the ONPRC Faculty Appointment & Promotions Committee, and Ambassador of the OHSU Center for Women’s Health. Dr. Stouffer has mentored over 40 graduate students and postdoctoral fellows, including M.D. resident researchers (e.g., Drs. T. Fisher, A. Hurliman, A. Lee in Ob-Gyn), and research fellows (e.g., Dr. M. Hibbert, Ob-Gyn; Dr. A. Bahar, Medicine). He was actively involved in mentoring beginning faculty in his division (including now established investigators, Drs. P. Grigsby, J. Hennebold, S. Mitalipov, O. Slayden, as well as recent additions such as Dr. J. Xu, a BIRCWH scholar and Dr. C. Bishop). Dr. Stouffer was also active in mentoring faculty in Ob-Gyn, including two previous WRHR fellows Drs. J. Jensen and A. Edelman, who are now renowned clinical scientists. As of August, 2015-2018, Dr. Stouffer served as scientific director of the NIH-funded WRHR (Women’s Health) Scholar Program in Ob-Gyn, OHSU.

 

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Areas of interest

  • Ovarian Biology
  • Infertility
  • Contraception
  • Reproductive Endocrinology

Education

  • B.S., Virginia Polytechnic Institute & State University 1971
  • Ph.D., Duke University 1975
  • Fellowship:

    • Staff Fellowship, National Institutes of Health, 1977

Honors and awards

  • Research Award, Society for the Study of Reproduction
  • Distinguished Researcher Award, American Society for Reproductive Medicine
  • Mentor Award, Medical Research Foundation of Oregon
  • John A. Resko Faculty Research and Mentoring Award, Oregon Health & Science University

Memberships and associations

  • Board of Directors, Society for the Study of Reproduction
  • President, Society for the Study of Reproduction
  • Board of Directors, Ovarian Workshop
  • Associate Editor, Molecular Human Reproduction
  • Associate Editor, Biology of Reproduction
  • Member and Chair, NIH REN Study Section
  • Society for the Study or Reproduction
  • American Society for Reproductive Medicine
  • American Primatology Society
  • International Society for Primatology
  • American Association for Advancement of Science

Publications

Selected publications

  • Structure, Function and Regulation of the Corpus Luteum. Stouffer, R.L. and Hennebold, J.D. In: Knobil and Neill’s Physiology of Reproduction (Plant, T.M. and Zeleznik, A.J., eds.) Elsevier Academic Press, Vol 1, p.1703-1726, 2014

  • Corpus Luteum Rescue in Nonhuman Primates and Women. Stouffer, R.L. and Hennebold, J.D. In: The Life Cycle of the Corpus Luteum (Meiden, R., ed) Springer International Publishing, p. 183-204, 2017.

  • Studies of AMH Production, Action and Regulation in the Primate Ovary: Insight into Human Folliculogenesis, Xu, J., Zelinski, M.B., and Stouffer, R.L. In: Anti-Mullerian Hormone. Biology, Role in Ovarian Function and Clinical Significance (Seifer, D.B. and Tal, R., eds) Nova Science Publishers, Inc., p. 33-46, 2016.

  • Nonhuman Primates: A Vital Model for Basic and Applied Research on Female Reproduction, Prenatal Development and Women's Health. Stouffer, R. L. and Woodruff, T. K. Inst Lab An Res J, Vol 58, No.2, p.281-294. 2017.

Publications

  • "Localization of steroidogenic enzymes in macaque luteal tissue during the menstrual cycle and simulated early pregnancy" Biology of Reproduction May 1997
  • "Are human luteinizing granulosa cells a site of action for progesterone and relaxin?" Fertility and Sterility  1990
  • "Investigation of binding sites for follicle-stimulating hormone and chorionic gonadotropin in human ovarian cancers" Journal of Clinical Endocrinology and Metabolism  1984
  • "Systematic determination of differential gene expression in the primate corpus luteum during the luteal phase of the menstrual cycle" Molecular Endocrinology May 2008
  • "Exposure of female macaques to western-style diet with or without chronic T in vivo alters secondary follicle function during encapsulated 3-dimensional culture" Endocrinology March 1 2015
  • "Luteinizing Hormone Acts Directly at Granulosa Cells to Stimulate Periovulatory Processes" Endocrine December 2003
  • "Towards germline gene therapy of inherited mitochondrial diseases" Nature January 31 2013
  • "Gonadotropin and steroid regulation of steroid receptor and aryl hydrocarbon receptor messenger ribonucleic acid in macaque granulosa cells during the periovulatory interval" Endocrinology  1999
  • "Ovarian surface epitheliectomy in the non-human primate" Human Reproduction June 2011
  • "Initiation of periovulatory events in primate follicles using recombinant and native human luteinizing hormone to mimic the midcycle gonadotropin surge" Journal of Clinical Endocrinology and Metabolism July 1994
  • "Intraluteal infusion of a prostaglandin synthesis inhibitor, sodium meclofenamate, causes premature luteolysis in rhesus monkeys" Endocrinology  1988
  • "Insulin and insulin-like growth factor stimulation of vascular endothelial growth factor production by luteinized granulosa cells" Journal of Clinical Endocrinology and Metabolism July 2007
  • "Hormonal regulation of steroidogenic enzyme expression in granulosa cells during the peri-ovulatory interval in monkeys" Molecular Human Reproduction January 2000
  • "Circulating levels of total angiopoietin-2 and the soluble Tie-2 receptor in women during ovarian stimulation and early gestation" Fertility and Sterility November 2006
  • "Injection of soluble vascular endothelial growth factor receptor 1 into the preovulatory follicle disrupts ovulation and subsequent luteal function in rhesus monkeys" Biology of Reproduction October 1 2002
  • "The Functions and Regulation of Cell Populations Comprising the Corpus Luteum during the Ovarian Cycle"  December 18 2003
  • "Human recombinant activin-A alters pituitary luteinizing hormone and follicle-stimulating hormone secretion, follicular development, and steroidogenesis, during the menstrual cycle in rhesus monkeys" Journal of Clinical Endocrinology and Metabolism July 1993
  • "Intraluteal infusions of prostaglandins of the E, D, I, and A series prevent PGF(2α)-induced, but not spontaneous, luteal regression in rhesus monkeys" Biology of Reproduction  1990
  • "Role of gonadotrophins and progesterone in the regulation of morphological remodelling and atresia in the monkey peri-ovulatory follicle" Human Reproduction  2000
  • "Reply" Human Reproduction December 2011
  • "Discovery of LH-regulated genes in the primate corpus luteum" Molecular Human Reproduction March 2005
  • "Evaluation of antral follicle growth in the macaque ovary during the menstrual cycle and controlled ovarian stimulation by high-resolution ultrasonography" American Journal of Primatology May 2009
  • "Endocrine and local control of the primate corpus luteum" Reproductive biology December 2013
  • "Activity and expression of different members of the caspase family in the rat corpus luteum during pregnancy and postpartum" American Journal of Physiology - Renal Fluid and Electrolyte Physiology November 2007
  • "Estrogen production by luteal cells isolated from rhesus monkeys during the menstrual cycle" Endocrinology  1980
  • "Stimulatory and inhibitory effects of prostaglandins on the gonadotropin-sensitive adenylate cyclase in the monkey corpus luteum" Prostaglandins and Other Lipid Mediators  1987
  • "The Sulawesi Crested Black Macaque (Macaca nigra) menstrual cycle" Biology of Reproduction  1992
  • "Cellular approaches to understanding the function and regulation of the primate corpus luteum" Seminars in Reproductive Medicine  1991
  • "Changes in [125I]labeled human chorionic gonadotropin (hCG) binding to porcine granulosa cells during follicle development and cell culture" Endocrinology  1976
  • "Effects of hyperandrogenemia and increased adiposity on reproductive and metabolic parameters in young adult female monkeys" American Journal of Physiology - Renal Fluid and Electrolyte Physiology June 1 2014

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