The principal investigator has had a long-term commitment to a career in academic medicine. Following the completion of a M.D.-Ph.D. degree at the University of Chicago, he is now completing training in an academic pathology residency at the University of Pennsylvania, with an emphasis in gynecologic pathology. The CIA will allow the candidate to bridge his research and clinical training and develop into an independent biomedical investigator. Research: The principal investigator proposes to study the regulation of steroidogenesis in the human trophoblast. He has purified a population of cells from human term placentae which, by structural features and steroidogenic activity, are trophoblasts. Immunochemical staining for hCG, hPL, low molecular weight keratin, vimentin and alpha-1 anti-chymotrypsin indicated that these cells are cytotrophoblasts. Preliminary findings suggest that they transform into synctialtrophoblasts in short-term culture with a concomitant 8-fold increase in progesterone synthesis and 3-9-fold increase in hCG production.
The aims of the proposed research are to determine 1) whether the syncytial elements form by cell fusion or endomitosis; 2) the temporal changes in steroidogenesis as syncytia form; and 3) define the factors (hormones or paracrines) which regulate steroidogenesis and syncytium formation in culture. Environment: The principal investigator will perform the proposed research under the guidance of Dr. Jerome Strauss, Director of the Division of Reproductive Biology (DRB), in the Department of Obstetrics and Gynecology and a member of the Department of Pathology and Laboratory Medicine. The Division of Reproductive Biology includes eight full time investigators whose research focuses on molecular and cellular aspects of reproduction. These investigators can be called upon for consultation. In addition to the facilities of the DRB, the facilities of the Department of Pathology and Laboratory Medicine, including the electron microscopy and immunocytochemical laboratories, will be available for this study.

Project Start
1985-12-01
Project End
1988-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Babalola, G O; Coutifaris, C; Soto, E A et al. (1990) Aggregation of dispersed human cytotrophoblastic cells: lessons relevant to the morphogenesis of the placenta. Dev Biol 137:100-8
Kliman, H J; Feinberg, R F; Haimowitz, J E (1990) Human trophoblast-endometrial interactions in an in vitro suspension culture system. Placenta 11:349-67
Kliman, H J; Coutifaris, C; Babalola, G O et al. (1989) The human trophoblast: homotypic and heterotypic cell-cell interactions. Prog Clin Biol Res 294:425-34
Feinberg, R F; Kao, L C; Haimowitz, J E et al. (1989) Plasminogen activator inhibitor types 1 and 2 in human trophoblasts. PAI-1 is an immunocytochemical marker of invading trophoblasts. Lab Invest 61:20-6
Kao, L C; Caltabiano, S; Wu, S et al. (1988) The human villous cytotrophoblast: interactions with extracellular matrix proteins, endocrine function, and cytoplasmic differentiation in the absence of syncytium formation. Dev Biol 130:693-702
Ulloa-Aguirre, A; August, A M; Golos, T G et al. (1987) 8-Bromo-adenosine 3',5'-monophosphate regulates expression of chorionic gonadotropin and fibronectin in human cytotrophoblasts. J Clin Endocrinol Metab 64:1002-9
Feinman, M A; Kliman, H J; Main, E K (1987) HLA antigen expression and induction by gamma-interferon in cultured human trophoblasts. Am J Obstet Gynecol 157:1429-34
Feinman, M A; Kliman, H J; Caltabiano, S et al. (1986) 8-Bromo-3',5'-adenosine monophosphate stimulates the endocrine activity of human cytotrophoblasts in culture. J Clin Endocrinol Metab 63:1211-7