The long range goal of this research is to define the role(s) of the TNF gene family in reproduction. New experimental approaches have been developed for the purpose of evaluating the functions of trophoblast cell TNFa that include use of knockout (KO) mice carrying deletions of the TNFa/LTa and TNF receptor (TNF-R) genes, and generation of mouse trophoblastic cell lines from these as well as normal mice. Preliminary experiments show that: 1) the TNF signaling system is critical to normal development of placental compartments, 2) TNF/TNF-R signaling is involved in gender-specific pathways that affect normal development, 3) trophoblastic cell lines derived from mouse placentas express the TNFa gene and, 4) under some conditions, trophoblastic cell lines are growth-inhibited by exogenous TNFa. Additional studies demonstrate that two other biologically-potent members of the TNF superfamily, FasL and Lt-beta, are expressed in the uteri and placentae of pregnant mice, and preliminary data strongly suggest that FasL has an important role in restricting maternal-fetal migration of activated hematopoietic cells.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Study Section
Reproductive Biology Study Section (REB)
Program Officer
Lock, Allan
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University of Kansas
Anatomy/Cell Biology
Schools of Medicine
Kansas City
United States
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Hunt, Joan S; Pace, Judith L; Gill, Ryan M (2010) Immunoregulatory molecules in human placentas: potential for diverse roles in pregnancy. Int J Dev Biol 54:457-67
Ka, Hakhyun; Hunt, Joan S (2003) Temporal and spatial patterns of expression of inhibitors of apoptosis in human placentas. Am J Pathol 163:413-22
Phillips, Teresa A; Ni, Jian; Hunt, Joan S (2003) Cell-specific expression of B lymphocyte (APRIL, BLyS)- and Th2 (CD30L/CD153)-promoting tumor necrosis factor superfamily ligands in human placentas. J Leukoc Biol 74:81-7
Audus, Kenneth L; Soares, Michael J; Hunt, Joan S (2002) Characteristics of the fetal/maternal interface with potential usefulness in the development of future immunological and pharmacological strategies. J Pharmacol Exp Ther 301:402-9
Phillips, T A; Ni, J; Hunt, J S (2001) Death-inducing tumour necrosis factor (TNF) superfamily ligands and receptors are transcribed in human placentae, cytotrophoblasts, placental macrophages and placental cell lines. Placenta 22:663-72
Bowen, J A; Hunt, J S (2000) The role of integrins in reproduction. Proc Soc Exp Biol Med 223:331-43
Hunt, J S; Petroff, M G; Burnett, T G (2000) Uterine leukocytes: key players in pregnancy. Semin Cell Dev Biol 11:127-37
Phillips, T A; Ni, J; Pan, G et al. (1999) TRAIL (Apo-2L) and TRAIL receptors in human placentas: implications for immune privilege. J Immunol 162:6053-9
Bowen, J A; Hunt, J S (1999) Expression of cell adhesion molecules in murine placentas and a placental cell line. Biol Reprod 60:428-34
Rasmussen, C A; Pace, J L; Banerjee, S et al. (1999) Trophoblastic cell lines generated from tumour necrosis factor receptor-deficient mice reveal specific functions for the two tumour necrosis factor receptors. Placenta 20:213-22

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