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.
