Research Interests:
Trophoblasts are the cells of the human placenta responsible for implantation of the embryo, maintenance of pregnancy and fetal-maternal metabolic and nutritional exchange. Work in Dr. Coutifaris' laboratory centers around elucidating the mechanism(s) regulating the differentiation of cytotrophoblasts towards the extravillous (invasive) versus the villous (non-invasive but hormonally active) phenotypes. Primary cultures of trophoblasts isolated from human placentae as well as several choriocarcinoma cell lines with different migratory, aggregating and fusing capacities are used as models for in vitro studies. Specifically, the investigative effort is directed towards understanding the roles of cell adhesion molecules (CAM's) and extracellular matrix receptors (integrins) in these morphogenetic processes. The main focus of the research is to analyze the interaction of these cell surface glycoproteins with the cytoskeleton and elucidate their role in specific gene activation, which, in turn, results in remodelling of the cell adhesion complex and leads to cellular fusion and syncytial trophoblast formation. In addition, the expression and cell-surface organization of integrins, which confer the migratory, invasive or stationary phenotypes to these cells is also being investigated. The long-term goal of these research efforts is to understand, at the molecular level, aspects of normal and pathologic trophoblast implantation.

The cellular and molecular mechanisms involved in the growth of human preantral follicles and the subsequent maturation of the oocyte to acquire competence to undergo meiosis remain largely unknown. Numerous studies have contributed to knowledge of these events in several animal species. The clinical application of this knowledge to the human is significant for the treatment of infertility, the improvement of the reproductive potential of women surviving childhood or early adulthood cancers as well as by its contribution to a basic understanding of reproductive events. In order to study the maturation of oocytes in vivo as well as in vitro, oocytes are retrieved from volunteers (women undergoing tubal ligations) at different times following hCG administration. In addition, a unique aspect of our studies involves excision of preantral follicles from ovarian tissue in order to construct culture systems that permit maturation of a competent gamete. A major goal is to define the extracellular factors that mediated the activation of apoptotic signals in granulosa during human follicular maturation in vivo and in vitro. An additional goal is to evaluate culture systems for the in vitro development of preantral. The effects of various growth factors and hormones on follicular and oocyte development are being assessed.

Recent Representative Publications:
McGovern PG, Myers ER, Silva S, Coutifaris C, Carson SA, Legro RS, Schlaff WD, Carr BR, Steinkampf MP, Giudice LC, Leppert PC, Diamond MP for the NICHD National Cooperative Reproductive Medicine Network. Absence of secretory endometrium after false-positive home urine luteinizing hormone testing. Fertil Steril 82:1273-77, 2004.

Myers ER, Silva S, Barnhart K, Groben PM, Richardson MS, Robboy SJ and Coutifaris C for the National Cooperative Reproductive Medicine Network: Inter- and Intraobserver Variability in the Histologic Dating of the Endometrium in Fertile and Infertile Women. Fertil Steril 82:1278-82, 2004.

Loret de Mola JR., Barnhart K., Kopf, GS., Heyner, S., Garside, W., Coutifaris, C.: Comparison of two culture systems for the in-vitro growth and maturation of mouse pre-antral follicles. Clin Exp Obstet &Gyn 31: 15-19, 2004.

Coutifaris C, Myers ER, Guzick DS, Diamond MP, Carson SA, Legro RS, McGovern PG, Schlaff WD,.Carr BR, Steinkampf MP, Silva S, Vogel DL and Leppert PC for the National Cooperative Reproductive Medicine Network: Histological Dating of Timed Endometrial Biopsy Tissue Is Not Related to Fertility Status. Fertil Steril 82:1264-72, 2004.

Coutifaris C, Omigbodun A, Coukos G The Fibronectin Receptor a5 Integrin Subunit Is Up-Regulated by Cell-Cell Adhesion via a Cyclic AMP-Dependent Mechanism: Implications for Human Trophoblast Migration Am J Obstet Gynecol 192:1240-55, 2005.

Legro RS, ER Myers , HX Barnhart, SA Carson, MP Diamond, BR Carr, MD, WD Schlaff, C Coutifaris, PG McGovern, NA Cataldo, MP Steinkampf, JE Nestler, G Gosman, LC Guidice, PC Leppert for the Reproductive Medicine Network: The Pregnancy in Polycystic Ovary Syndrome Study: Baseline Characteristics of the Randomized Cohort including Racial Effects. Fertil Steril 86:914-33., 2005.

Gracia CR, Sammel MD, Coutifaris C, Guzick DS, Barnhart KT: Environmental Exposures and Male Infertility. Am J Epidemiol 162: 729-733, 2005.

Chung, K, Sammel MD, Coutifaris C, Chalian R, Lin K, Castelbaum AJ, Freedman MF, Barnhart KT: Defining the rise of serum hCG in viable pregnancies achieved through use of IVF. Human Reprod 21:823-28, 2006.

Chung, K., C. Coutifaris, et al. "Factors influencing adverse perinatal outcomes in pregnancies achieved through use of in vitro fertilization." Fertil Steril 86: 1634-41. 2006.

McGovern, P. G., R. S. Legro, et al. "Utility of screening for other causes of infertility in women with "known" polycystic ovary syndrome." Fertil Steril 87(2): 442-4, 2007.

Legro, R. S., Barnhart, H. X., Schlaff, W. D., Carr, B. R., Diamond, M. P., Carson, S. A., Steinkampf, M. P., Coutifaris, C., McGovern, P. G., Cataldo, N. A., Gosman, G. G., Nestler, J. E., Giudice, L. C., Leppert, P. C., and Myers, E. R. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 356, 551-66, 2007.

Lin, K., and Coutifaris, C. In vitro fertilization in the polycystic ovary syndrome patient: an update. Clin Obstet Gynecol 50, 268-76, 2007.

Rolaki, A., Coukos, G., Loutradis, D., DeLisser, H. M., Coutifaris, C., and Makrigiannakis, A. Luteogenic hormones act through a vascular endothelial growth factor-dependent mechanism to up-regulate alpha 5 beta 1 and alpha v beta 3 integrins, promoting the migration and survival of human luteinized granulosa cells. Am J Pathol 170, 1561-72, 2007.