The objective of the proposed research is to elucidate cellular and biochemical alterations in the placenta which underlie the feto-placental growth retardation associated with exposure to polyromatic hydrocarbons (PAH) during pregnancy. The first specific aim will investigate whether exposure of human placental cells to benzo(a)pyrene (BP) and related PAH compounds alters the differentiation to trophoblast cells. Experiments are proposed to quantitate the effects of BP on cytotrophoblast fusion to form syncytia and on the expression of the biochemical markers of differentiation, chorionic gonadotrophin (hCG), placental lactogen (hPL), and pregnancy-specific B1 glycoprotein (hPSBG). The effects of BP on EGF receptors will be examined to determine if down-regulation of receptors is correlated temporally with changes in differentiation state. The second specific aim will examine rat placenta to determine whether exposure to prototype PAH compounds alters growth factor production or receptor function at the maternal-fetal interface. Studies will determine whether BP, B-naphthoflavone (BNF) 3-methylcholanthrene, (3MC) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have direct effects on trophoblast cells, or whether trophoblast cells are altered indirectly by changes in cytokine production from maternal decidua. The final specific aim is to evaluate whether cytokines, particularly IL-1, modulate the induction of cytochrome P-450IA1 in placental cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES004435-05
Application #
3252593
Study Section
Toxicology Subcommittee 2 (TOX)
Project Start
1987-07-01
Project End
1995-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Florida
Department
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
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