Geburtshilfe Frauenheilkd 2006; 66 - FV_G_02_09
DOI: 10.1055/s-2006-952301

Comparative proteomic analysis of II trimester human amniotic fluid (AF) of normal and severe preeclampsia evolved pregnancies: identification of a new early marker of the pathology in a pilot study.

A Fruscalzo 1, C Vascotto 2, AM Salzano 3, C D’Ambrosio 3, A Scaloni 3, C di Loreto 4, G Tell 2, D Marchesoni 5, F Quadrifoglio 2
  • 1Clinica Ginecologia Ostetricia Università di Udine, Udine, Italien
  • 2Department of Biomedical Sciences and Technologies, University of Udine, Udine, Italy
  • 33Proteomic and Mass Spectrometry Laboratory, ISPAAM, National Research Council, Neaples, Italy
  • 4Department of Anatomic Pathology, University of Udine, Udine, Italy
  • 5Università di Udine, Ginecologia ed Ostetricia, Udine, Italy

Introduction: Preeclampsia is a life threatening disorder of pregnancy affecting about 2.5–3% of women and uterine artery Doppler ultrasound during the second trimester is nowadays the only useful screening test. Proteomic analysis allows to analyze the proteic profile of normal and affected subjects and to appreciate any difference in protein concentration or posttranslational modifications for new markers discovery.

Materials & methods: Between April 2003 and August 2004, 446 women underwent amniocentesis in the II trimester of pregnancy for genetic prenatal diagnosis. 2ml of each AF sample were designated for proteomic analysis and each pregnancy was followed until termination. Five patients who developed a severe preeclampsia and five women with uncomplicated pregnancy were selected. The 2-DE AF gels were compared in order to find out possible differential protein expression and MS was performed to define the nature of the differentially expressed proteins and their posttranslational modifications.

Results: Comparative analysis revealed a significant quantitative difference in protein spots intensity between healthy and preeclamptic samples, corresponding to the dimeric and monomeric forms of transthyretin (TTR), an homotetrameric protein, while its total amount was not significantly different. Evaluation of the normalized volume values revealed that the amount of the dimeric form of TTR is significantly decreased in association with preeclampsia in favour of the monomeric form. MS analysis showed that the destabilization of the dimeric form is the result of an oxidative stress which modifies the cysteine in position 10 of TTR.

Conclusion: The finding of a quantitative difference in the protein composition of the second trimester AF seems to be related to an oxidative stress situation and to the future development of preeclampsia; hence it could be used as an early marker of disease in women who undergo amniocentesis for chromosomal prenatal diagnosis.