Specific peptides identified by mass spectrometry in placental tissue from pregnancies complicated by early onset preeclampsia attained by laser capture dissection.
Preeclampsia is a common pregnancy-specific syndrome that is diagnosed by the appearance of both increased blood pressure and proteinuria. Preeclampsia is associated with significant fetal and maternal morbidity and mortality. Although the etiology of preeclampsia is unknown, it is evident that abnormal placentation and trophoblast metabolism plays an important role. We therefore analyzed, identified, and verified specific proteins of villous trophoblast and villous stroma in small numbers of microdissected cells (approximately 125 cells) from seven placentas of women with pregnancies complicated by preeclampsia (cases) and seven uncomplicated pregnancies (controls). Tryptic peptide profiling by MALDI-TOF MS was used for comparison and identification of significantly expressed peptides. The data were analyzed by ClinProTools (Bruker Daltonics) and by principal component analysis. Subsequently, a subset of placental tissues were homogenized and separated on a NanoLC system to obtain sequencing information (MS/MS spectra). We identified specific peptide patterns in the different cell types: villous stroma and trophoblast cells and differences in these cells of placentas from women with pregnancies complicated by early compared to late onset preeclampsia (<34 and >34 wk gestation, respectively) and controls. Principal component analysis revealed significant differences between the groups. The comparison with placental tissue after preterm delivery with unknown cause revealed that placental peptide patterns in early onset preeclampsia could not be explained by preterm delivery per se. Subsequently, specific, discriminating proteins for early onset preeclampsia compared to controls were identified including calcyclin, surfeit locus protein, and choriomammotropin A precursor. The expression of calcyclin was verified in early onset preeclamptic placental sections by immunohistochemistry. These data suggest that in early onset preeclampsia trophoblastic choriomammotropin regulation is abnormal, possibly through abnormal calcyclin expression and regulation.
Department of Obstetrics and Gynecology/Division Obstetrics and Prenatal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Obstetrics and Gynecology, Medical Center Haaglanden, The Hague, The Netherlands.
Christianne J M
CJ
de Groot
Coşkun
C
Güzel
Régine P M
RP
Steegers-Theunissen
M
M
de Maat
Pieter
P
Derkx
Eva-Maria
EM
Roes
Ron M A
RM
Heeren
Theo M
TM
Luider
Eric A P
EA
Steegers