PARENT SESSION
PLATFORM SESSION 8. TROPHOBLAST DEVELOPMENT AND FUNCTION AND CERVIX REMODELING

Monday, August 2, 2004
2:00 PM–4:00 PM
Buchanan A203
Chair: Fuller W. Bazer Co-Chair: Shaye Lewis

(277) AN IN VIVO APPROACH TO INVESTIGATE THE REGULATION OF TROPHOBLAST CELL INVASION.

Arroyo, Juan ¹, Ain, Rupasri¹, Soares, Michael¹, ¹ Institute of Maternal-Fetal Biology and the Departments of Molecular & Integrative Physiology and Obstetrics & Gynecology, Kansas City, KS

ABSTRACT- Intrauterine trophoblast cell invasion is an essential part of hemochorial placentation. Aberrant trophoblast cell invasion has been associated with pathologies including preeclampsia and fetal growth restriction. In this study, we describe an in vivo method to assess trophoblast cell invasion using a transgenic rat model (R26-hAP), constitutively expressing heat stable human placental alkaline phosphatase (AP). Wild-type female rats were mated with R26-hAP male rats and sacrificed during the second half of pregnancy or following exposure to hypoxia or treatment with dexamethasone. Heat stable AP activity associated with the invasive transgenic trophoblast cells was monitored in the wild-type uterine mesometrial compartment and used as a quantitative index of trophoblast cell invasion. The unique expression patterns of cytokeratins and prolactin family genes by invasive trophoblast cells were utilized to validate the method. Trophoblast cell invasion exhibited a gestation-dependent profile with a peak in invasion between days 18-20 of pregnancy. Maternal hypoxia and dexamethasone treatment both decreased the trophoblast cell invasion but had very different impacts on placental and fetal development. Growth of the placenta and fetus were negatively impacted by maternal dexamethasone but were not significantly affected by maternal hypoxia. In all cases, intrauterine trophoblast cell invasion as assessed by monitoring heat stable AP activity of the transgenic trophoblast cells coincided with cytokeratin and prolactin family gene expression patterns. In summary, we have devised a simple in vivo method for assessing intrauterine trophoblast cell invasion. This technique should facilitate the discovery of endogenous regulatory mechanisms controlling trophoblast cell invasion and should represent an effective method of testing the impact of various environmental stressors on an essential part of hemochorial placentation. (Supported by HD20676, HD39878, Hall Family Foundation)

KEY WORDS: Preeclampsia, Hypoxia, Trophoblast Invasion, Hemochorial Placentation