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.
 

Proper ovarian function depends on highly orchestrated molecular events that control the development of a pre-ovulatory follicle during the first half of the menstrual cycle, its rupture midcycle to allow for the release of a fertilizable oocyte, and the subsequent development of the corpus luteum from the remnants of the ruptured follicle.  The newly formed corpus luteum produces the steroid hormone progesterone, which is required for the maintenance of pregnancy if fertilization occurs.  In the absence of fertilization, the corpus luteum regresses and progesterone production ceases, which in turn, allows for the initiation of the next menstrual cycle.  While the hormonal signals produced by the pituitary responsible for controlling ovarian function have received considerable attention, the intraovarian processes that they regulate are only poorly characterized.  Thus, Dr. Hennebold's laboratory team has utilized recently developed molecular and genomic approaches to systematically identify novel or previously unappreciated processes that contribute to proper ovarian function.
 
One particular area of interest for Dr. Hennebold's research team includes the characterization of the molecular and cellular events necessary for the development, function, and regression of the corpus luteum.  Using techniques that allow for the identification of nearly all differentially expressed mRNAs, Dr. Hennebold and his group have systematically determined which genes change in expression within the corpus luteum throughout the luteal phase.  From such studies, it was discovered that genes involved in the synthesis, metabolism, and response to prostaglandins are dynamically regulated in the primate corpus luteum through the luteal phase.  As prostaglandins are potent bioactive lipids capable of regulating numerous cellular activities, these results suggest that they may be critical for luteal physiology.  As such, the focus of the Hennebold laboratory is to determine what specific role prostaglandins play in regulating cellular function within the primate corpus luteum.  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.

Another 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.  These events, leading to ovulation, require significant cellular reorganization and extracellular matrix remodeling.  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 cellular and extracellular matrix remodeling 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 results of these studies may lead to the development of novel non-hormonal forms of contraception for women.

Key Publications

Peluffo MC, Hennebold JD, Stouffer RL, and Zelinski MB (2013). Oocyte maturation and in vitro hormone production in small antral follicles (SAFs) isolated from rhesus monkeys. J Assist Reprod Genet. 30:353-359. PMC3607688.

Adam M, Saller S, Ströb, S, Hennebold JD, Dissen G, Ojeda S, Stouffer RL, Berg D, Berg U, Mayerhofer A. (2012). Decorin is a part of the extracellular matrix in the human and nonhuman primate ovary and corpus luteum and activates epidermal growth factor receptor signaling in human luteinized granulosa cells. Human Reprod. 27:3249-50. 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. Epub. PMID: 22902348

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

Shaw KA, Hennebold JD, Edelman AB. (2012). 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. Epub. PMID: 23218850

 

See a full listing of Dr. Hennebold's publications