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Submitted on July 12, 2007
Accepted on October 12, 2007
Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71130
* To whom correspondence should be addressed. E-mail: ywang1{at}lsuhsc.edu.
Context: Increased productions of anti-angiogenic factors sEng and sFlt-1 by the placenta contribute to the pathophysiology in preeclampsia (PE).
Objective: To determine the differences in Eng, Flt-1 and PlGF expressions between normal and PE placentas and sEng, sFlt-1 and PlGF production by trophoblasts (TC) cultured under lowered oxygen conditions.
Methods: TCs isolated from normal and PE placentas were cultured under regular (5%CO2/air) and lowered (2%O2/5%CO2/93%N2) oxygen conditions. sEng, sFlt-1, and PlGF productions were determined by ELISA. Protein expressions for endoglin, Flt-1, and PlGF in the placental tissues were accessed by immunohistochemical staining and Western blot analysis. Deglycosylated endoglin, Flt-1 and PlGF protein expressions in placental tissues were also examined.
Results: 1) PE-TCs produced significantly more sEng, sFlt-1 and PlGF compared to those from normal-TCs, P< 0.05; 2) Under lowered oxygen conditions, PE-TCs, but not normal-TCs, released more sEng and sFlt-1. In contrast, both normal- and PE-TCs released less PlGF, P< 0.05; 3) Enhanced expressions of endoglin and Flt-1, as well as glycosylated endoglin and Flt-1, were observed in PE placentas; and 4) Immunoblot also revealed that TCs released glycosylated sFlt-1, but not sEng, in culture.
Conclusions: PE-TCs produce more sEng, sFlt-1 and PlGF than normal-TCs. Lowered oxygen conditions promote sEng and sFlt-1, but reduce PlGF, productions by PE-TCs. More glycosylated sEng and sFlt-1 are present in PE placentas. Trophoblasts release glycosylated sFlt-1, but unglycosylated sEng, in culture.
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