Early changes of placenta-derived messenger RNA in maternal plasma – potential value for preeclampsia prediction?

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Objective: the pourpose of the study was to determine if there are any differences between placenta derived plasmatic levels of messenger RNA in normal and future preeclamptic pregnancies and if these placental transcripts can predict preeclampsia long before clinical onset

Study design: we compared plasmatic expression of two placental transcripts from 12 women who ultimately developed preeclampsia with 224 controlled subjects, at the end of the first trimester of pregnancy. After multiplse-of-the-median conversion of markers we developed a multivariate model using logistic regression to determine preeclampsia risk.

Results: we found lower multiples of the median values for both placental transcripts (mRNA corresponding to placental growth factor and pregnancy associated plasmatic protein A) in cases who ultimately developed preeclampsia and the multivariate model we obtained offered a preeclampsia detection rate of 75% at 10% false positive rate.

Conclusion: specific early changes of placenta-derived messenger RNA could be used as preeclampsia predictors.

1. Osungbade KO, Ige OK. Public Health Perspectives of Preeclampsia in Developing Countries: Implication for Health System Strengthening. J Pregnancy. 2011; 2011: 481095.

2. Madazli R, Bulut B, Tuten A, Aydin B, Demirayak G, Kucur M. First-trimester maternal serum metastin, placental growth factor and chitotriosidase levels in pre-eclampsia. Eur J Obstet Gynecol Reprod Biol. 2012 Oct;164(2):146-9. DOI: 10.1016/j.ejogrb.2012.06.016

3. Vitoratos N, Hassiakos D, Iavazzo C. Molecular mechanisms of preeclampsia. J Pregnancy. 2012; 2012:298343. DOI: 10.1155/2012/145487 DOI: 10.1155/2012/298343

4. Akolekar R, Zaragoza E, Poon LC, Pepes S, Nicolaides KH. Maternal serum placental growth factor at 11 + 0 to 13 + 6 weeks of gestation in the prediction of pre-eclampsia. Ultrasound Obstet Gynecol. 2008 Nov;32(6):732-9. DOI: 10.1002/uog.6244

5. Bujold E, Romero R, Chaiworapongsa T, Kim YM, Kim GJ, Kim MR, et al. Evidence supporting that the excess of the sVEGFR-1 concentration in maternal plasma in preeclampsia has a uterine origin. J Matern Fetal Neonatal Med. 2005 Jul;18(1):9-16. DOI: 10.1080/14767050500202493

6. Levine RJ, Lam C, Qian C, Yu KF, Maynard SE, Sachs BP, et al. Soluble endoglin and other circulating anti-angiogenic factors in preeclampsia. N Engl J Med. 2006 Sep 7;355(10):992-1005. DOI: 10.1056/NEJMoa055352

7. Fialova L, Malbohan IM. Pregnancy-associated plasma protein A (PAPP-A): theoretical and clinical aspects. Bratisl Lek Listy. 2002;103(6):194-205.

8. Youssef A, Righetti F, Morano D, Rizzo N, Farina A. Uterine artery Doppler and biochemical markers (PAPP-A, PIGF, sFlt-1, P-selectin, NGAL) at 11 + 0 to 13 + 6 weeks in the prediction of late (> 34 weeks) pre-eclampsia. Prenat Diagn. 2011 Dec;31(12):1141-6.

9. Di Lorenzo G, Ceccarello M, Cecotti V, Ronfani L, Monasta L, Vecchi Brumatti L, et al. First trimester maternal serum PIGF, free β-hCG, PAPP-A, PP-13, uterine artery Doppler and maternal history for the prediction of preeclampsia. Placenta 2012 Jun; 33(6): 495-501. DOI: 10.1016/j.placenta.2012.03.003

10. Espinoza J, Romero R, Nien JK, Gomez R, Kusanovic JP, Gonçalves LF, et al. Identification of patients at risk for early onset and/or severe preeclampsia with the use of uterine artery Doppler velocimetry and placental growth factor. Am J Obstet Gynecol. 2007 Apr;196(4):326.e1-13. DOI: 10.1016/j.ajog.2006.11.002

11. Akolekar R, Syngelaki A, Poon L, Wright D, Nicolaides KH. Competing risks model in early screening for preeclampsia by biophysical and biochemical markers. Fetal Diagn Ther. 2013;33(1):8-15. DOI: 10.1159/000341264

12. Laresqoiti-Servitje E. A leading role for the immune system in the pathopysiology of preeclampsia. J Leukoc Biol 2013 Aug; 94 (2):247-57. DOI: 10.1189/jlb.1112603

13. Cali U, Cavkaytar S, Sirvan L, Danisman N. Placental apoptosis in preeclampsia, intrauterine growth retardation and HELLP syndrome: an immunohistochemical study with caspase-3 and bcl-2. Clin Exp Obstet Gynecol. 2013; 40 (1): 45-8.

14. Ng EK, Tsui NB, Lau TK, Leung TN, Chiu RW, Panesar NS, et al. mRNA of placental origin is readily detectable in maternal plasma. Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4748-53. DOI: 10.1073/pnas.0637450100

15. Tsui NB, Wong CS, Chow KC, Lo ES, Cheng YK. Investigation of biological factors influencing the placental mRNA profile in maternal plasma. Prenat. Diagn. 2014, 34, 251–258. DOI: 10.1002/pd.4300

16. Farina A. The role of RNAs and microRNAs in non-invasive prenatal diagnosis. J Clin Med 2014; 3: 440-452. DOI: 10.3390/jcm3020440

17. Okazaki S, Sekizawa A, Purwosunu Y, Iwasaki M, Farina A, Okai T. Measurement of mRNA of trophoblast-specific genes in cellular and plasma components of maternal blood. J Med Genet. 2006 Sep;43(9):e47. DOI: 10.1136/jmg.2005.040634

18. Heung MM, Jin S, Tsui NB, Ding C, Leung TY, Lau TK, et al. Placenta-derived fetal specific mRNA is more readily detectable in maternal plasma than in whole blood. PLoS One. 2009 Jun 10; 4(6): e5858. DOI: 10.1371/journal.pone.0005858

19. Sekizawa A, Purwosunu Y, Farina A, Shimizu H, Nakamura M, Wibowo N, et al. Prediction of pre-eclampsia by an analysis of placenta-derived cellular mRNA in the blood of pregnant women at 15–20 weeks of gestation. BJOG 2010, 117, 557–564. DOI: 10.1111/j.1471-0528.2010.02491.x

20. Farina A, Zucchini C, Sekizawa A, Purwosunu Y, de Sanctis P, Santarsiero G, et al. Performance of messenger RNAs circulating in maternal blood in the prediction of preeclampsia at 10–14 weeks. Am. J. Obstet. Gynecol. 2010, 203, e1–e7. DOI: 10.1016/j. ajog.2010.07.043

22. Purwosunu Y, Sekizawa A, Okazaki S, Farina A, Wibowo N, Nakamura M, et al. Prediction of preeclampsia by analysis of cell-free messenger RNA in maternal plasma. Am. J. Obstet. Gynecol. 2009, 200, doi:10.1016/j.ajog.2008.11.035. DOI: 10.1016/j.ajog.2008.11.035

23. Anton L, Olarerin-George AO, Schwartz N, Srinivas S, Bastek J, Hogenesch JB, et al. miR-210 inhibits trophoblast invasion and is a serum biomarker for preeclampsia. Am J Pathol. 2013 Nov;183(5):1437-45. DOI: 10.1016/j.ajpath.2013.07.021

Revista Romana de Medicina de Laborator

Romanian Journal of Laboratory Medicine

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