OHSU

Jon D. Hennebold

Within the past several years, the resultant data generated from genome-sequencing projects have provided scientists with the opportunity to identify most, if not all, genes that determine the physiology of a particular organism.  For reproductive biologists, such genomic databases allow for the systematic identification and characterization of molecular pathways that are critical for fertility.  The information gained from such studies can be used to further our understanding of the causes of infertility and diseases of the reproductive tract, as well as to identify novel targets for the control of fertility.
 

A main area of interest for Dr. Hennebold involves identifying and characterizing the molecular events that are necessary for follicle rupture and detachment of the oocyte from the inner cell layer of the follicle, as well as the development and regression of the corpus luteum. Ovulation, luteal formation and luteal regression require significant cellular reorganization and extracellular matrix remodeling. For ovulation to occur, detachment and release of the oocyte must be preceded by loss of cell-to-cell contacts and formation of an extracellular matrix between the cells surrounding the oocyte. The individual genes responsible for initiating and executing these processes have yet to be fully elucidated. Recent genomic studies conducted in a collaborative effort involving Dr. Hennebold and the Center's Dr. Richard Stouffer have led to the identification of genes whose expression increases through the period preceding follicle rupture and, as a consequence, are likely involved in the requisite molecular and cellular events necessary for ovulation. Currently, Dr. Hennebold's team and colleagues are studying the exact contribution these genes play in allowing for the rupture of the ovulatory follicle and the release of the oocyte. The goal of these studies is the development of novel approaches to control fertility, including the identification of processes that promote fertility in women seeking to have children or for the development of non-hormonal female contraceptives. Dr. Hennebold and his group have also systematically identified those genes whose corresponding mRNA levels change within the corpus luteum through its development, period of peak progesterone production, and regression. The end result of these studies will be a better understanding of events necessary for luteal formation and function, as well as the underlying cause of infertility that is related to luteal dysfunction or insufficiency.

Dr. Hennebold also oversees the activities of the ONPRC Assisted Reproductive Technologies (ART) Core, which supports studies that aim to advance our understanding of reproduction and development in clinically relevant model systems. ART Core services include, but are not limited to, controlled ovarian stimulation, oocyte retrieval, granulosa cells and follicular fluid, sperm, IVF, ICSI, embryo transfer, ultrasonography, and oocyte/embryo culture. In addition to its regular services, the Core seeks to develop new ART reagents, services, and expertise that advance studies of reproductive processes. The Core’s technology development objectives include identifying methods to optimize in vitro fertilization/ART success rates in terms of embryo generation and development, advancing ARTs in species that are valuable research models and evaluating recently developed molecular techniques that likely represent an efficient means to generate relevant disease models.

 

BIOGRAPHY

Dr. Hennebold is an Associate Scientist and Interim Chief of the Division of Reproductive & Developmental Sciences at the Center. He is also an adjunct faculty member in the Departments of Obstetrics & Gynecology and Physiology & Pharmacology at OHSU. Dr. Hennebold currently serves as the Director of the ONPRC Assisted Reproductive Technologies (ART) Core, which supports research activities involving nonhuman primate studies of reproductive biology. He received his Ph.D. in immunology and cell biology at the Department of Pathology, University of Utah School of Medicine in 1996. Dr. Hennebold then conducted his postdoctoral training in reproductive sciences at the University of Utah Department of Obstetrics & Gynecology. In 2000, he joined ONPRC as a Staff Scientist and was promoted to Assistant Scientist in 2003. 

 

KEY PUBLICATIONS

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

Hanna, CB, Hennebold, JD. (2014). Ovarian germline stem cells: an unlimited source of oocytes? Fertil Steril 101:20-30. PMC3926438

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

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.

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

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

Shaw KA, Hennebold JD, Edelman AB. (2013). Effect of a combined estrogen and progesterone oral contraceptive on circulating adipocytokines adiponectin, resistin and DLK-1 in normal and obese female rhesus monkeys. Contraception 88:177-82.  PMC3919957

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

Bogan, RL, Debarber, AE, Hennebold, JD. (2012). Liver x receptor modulation of gene expression leading to proluteolytic effects in primate luteal cells. Biol Reprod. 86:89. PMC3316272

Edelman AB, Jensen JT, Doom C, Hennebold JD. (2012). Impact of the prostaglandin synthase-2 inhibitor celecoxib on ovulation and luteal events in women. Contraception. 87:352-7. PMC4040982

Peluffo, MC, Ting, AY, Zamah, AM, Conti, M, Stouffer, RL, Zelinski, MB, Hennebold, JD. (2012). Amphiregulin promotes the maturation of oocytes isolated from the small antral follicles of the rhesus macaque. Hum Reprod. 27:2430-7. PMC3398676

 

See a full listing of Dr. Hennebold's publications