Intrauterine growth retardation (IUGR) results in infants which are small for gestational age and is associated with an increased incidence of perinatal morbidity and mortality. Inadequate placental growth and function is one possible cause of IUGR. Unfortunately, a basic understanding of the regulation of human placental growth is poorly defined. Studies in the mouse have shown that hematopoietic growth factors stimulate placental cell proliferation in vitro. In addition, receptors for hematopoietic growth factors including colony stimulating factor-1 (CSF-1), granulocyte-macrophage stimulating factor (GM-CSF), and interleukin-6 (IL-6) are present in trophoblast. Since CSF-1, GMCSF, and IL-6 are produced in cultured human placental explants in vitro these cytokines may be important regulators of placental growth and function. Interleukin-1 (IL-l) is produced by decidua during pregnancy, and is known to stimulate the production of CSF- 1, GM-CSF, and IL-6 by mesenchymal cell types. Consequently, we hypothesize that maternal decidual IL-1 may stimulate placental mesenchymal cell production of CSF-1, GM-MF, and IL-6 which in turn would regulate placental trophoblast growth and function. This hypothesis win be tested with regard to the following specific aims: 1) To determine if IL-l can regulate placental cytokine production by studying the regulation of CSF-1, GM-CSF, and IL-6 mRNA expression and protein synthesis by IL-l in intact second trimester placental villi and placental villous core mesenchymal cells in vitro. 2) To evaluate the role of CSF-1, GM-CSF, and IL-6 as growth factors for the placenta by examining the bioproliferative effects of these cytokines on isolated placental trophoblast in vitro. 3) To determine if amniotic fluid and maternal serum levels of immunoreactive CSF-1 are clinically correlated with the development and diagnosis of IUGR. 4) To determine if basal and IL-l induced mRNA expression and protein production rates of CSF-1, GM-CSF, and IL-6 are decreased in placentas from term pregnancies affected by IUGR. The findings from these studies will delineate whether these cytokines regulate the growth and function of the developing placenta, and the potential role of these cytokines in the pathophysiology of IUGR.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HD029023-03
Application #
2201534
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1993-01-01
Project End
1997-12-31
Budget Start
1995-01-01
Budget End
1995-12-31
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298