Placental productions and expressions of soluble endoglin, soluble fms-like tyrosine kinase receptor-1, and placental growth factor in normal and preeclamptic pregnancies.
BACKGROUND
Increased production of antiangiogenic factors soluble endoglin (sEng) and soluble fms-like tyrosine kinase receptor-1 (sFlt-1) by the placenta contributes to the pathophysiology in preeclampsia (PE).


OBJECTIVE
Our objective was to determine the differences in endoglin (Eng), fms-like tyrosine kinase receptor-1 (Flt-1), and placental growth factor (PlGF) expressions between normal and PE placentas and sEng, sFlt-1, and PlGF production by trophoblast cells (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 Eng, Flt-1, and PlGF in the placental tissues were accessed by immunohistochemical staining and Western blot analysis. Deglycosylated Eng, Flt-1, and PlGF protein expressions in placental tissues were also examined.


RESULTS
PE TCs produced significantly more sEng, sFlt-1, and PlGF compared with those from normal TCs (P < 0.05). 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). Enhanced expressions of Eng and Flt-1, as well as glycosylated Eng and Flt-1, were observed in PE placentas. 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.
Gu
Yang
Y
Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center-Shreveport, PO Box 33932, Shreveport, Louisiana 71130, USA.
Lewis
David F
DF
Wang
Yuping
Y
D015703:Antigens, CD / Q000096:biosynthesis*; D015153:Blotting, Western; D000071063:Endoglin; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D010920:Placenta / Q000378:metabolism*; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000096:biosynthesis*; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D014327:Trophoblasts / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis*
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011956:Receptors, Cell Surface; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1