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.