Semaphorin 3F expression is reduced in pregnancy complicated by preeclampsia. An observational clinical study

PLoS One. 2017 Mar 28;12(3):e0174400. doi: 10.1371/journal.pone.0174400. eCollection 2017.


Background and objective: Preeclampsia is a systemic disorder, affecting 2-10% of pregnancies, characterized by a deregulated pro- and anti-angiogenic balance. Semaphorin 3F is an angiogenesis inhibitor. We aimed to investigate whether semaphorin 3F expression is modulated in preeclampsia.

Design, setting, participants, and measurements: We performed two observational single center cohort studies between March 2013 and August 2014. In the first we enrolled 110 consecutive women, undergoing an elective cesarean section; in the second we included 150 consecutive women undergoing amniocentesis for routine clinical indications at 16-18 week of gestation. Semaphorin 3F concentration was evaluated in maternal peripheral blood, venous umbilical blood and amniotic fluid, along with its placenta protein expression at the time of delivery in the first study group and in the amniotic fluid at 16-18 weeks of gestation in the second study group.

Results: In the first study 19 patients presented at delivery with preeclampsia. Semaphorin 3F placenta tissue expression was significantly reduced in preeclampsia. In addition, semaphorin 3F level at delivery was significantly lower in serum, amniotic fluid and venous umbilical blood of preeclamptic patients compared with normal pregnant women. In the prospective cohort study 14 women developed preeclampsia. In this setting, semaphorin 3F amniotic level at 16-18 weeks of gestation was reduced in women who subsequently developed preeclampsia compared to women with a normal pregnancy. ROC curve analysis showed that semaphorin 3F amniotic levels could identify women at higher risk of preeclampsia.

Conclusions: Semaphorin 3F might represent a predictive biomarker of preeclampsia.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Amniotic Fluid / chemistry
  • Cohort Studies
  • Female
  • Fetal Blood / chemistry
  • Humans
  • Infant, Newborn
  • Membrane Proteins / analysis*
  • Membrane Proteins / blood*
  • Nerve Tissue Proteins / analysis*
  • Nerve Tissue Proteins / blood*
  • Placenta / pathology*
  • Pre-Eclampsia / blood*
  • Pre-Eclampsia / pathology*
  • Pregnancy


  • Membrane Proteins
  • Nerve Tissue Proteins
  • SEMA3F protein, human

Grants and funding

The study was supported by the Italian Ministry of Health (Ministero della Salute (IT)), grant no. RF-2009-1471624 to GG and by the Italian Ministry of Education, University and Research (Ministero dell’Istruzione, dell’Università e della Ricerca (IT)), grant no. RBNE08BNL7 to GSN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.