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The placenta in fetal death: molecular evidence of dysregulation of inflammatory, proliferative, and fetal protective pathways.
Nardi, Eleonora; Seidita, Isabelle; Abati, Isabella; Donati, Chiara; Bernacchioni, Caterina; Castiglione, Francesca; Serena, Caterina; Mecacci, Federico; Bloise, Enrrico; Petraglia, Felice.
Afiliación
  • Nardi E; Pathology, Department of Health Science, University of Florence, Florence, Italy.
  • Seidita I; Lipid Cell Signaling and Biology Lab, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
  • Abati I; Obstetrics and Gynecology, Department of Experimental, Clinical and Biomedical Sciences, Careggi University Hospital, University of Florence, Florence, Italy.
  • Donati C; Lipid Cell Signaling and Biology Lab, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
  • Bernacchioni C; Lipid Cell Signaling and Biology Lab, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
  • Castiglione F; Pathology, Department of Health Science, University of Florence, Florence, Italy.
  • Serena C; Obstetrics and Gynecology, Department of Experimental, Clinical and Biomedical Sciences, Careggi University Hospital, University of Florence, Florence, Italy.
  • Mecacci F; Obstetrics and Gynecology, Department of Experimental, Clinical and Biomedical Sciences, Careggi University Hospital, University of Florence, Florence, Italy.
  • Bloise E; Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil; Department of Physiology, University of Toronto, Toronto, ON, Canada.
  • Petraglia F; Obstetrics and Gynecology, Department of Experimental, Clinical and Biomedical Sciences, Careggi University Hospital, University of Florence, Florence, Italy. Electronic address: felice.petraglia@unifi.it.
Am J Obstet Gynecol ; 2024 Jun 20.
Article en En | MEDLINE | ID: mdl-38908653
ABSTRACT

BACKGROUND:

It is estimated that over 2 million cases of fetal death occur worldwide every year, but, despite the high incidence, several basic and clinical characteristics of this disorder are still unclear. Placenta is suggested to play a central role in fetal death. Placenta produces hormones, cytokines and growth factors that modulate functions of the placental-maternal unit. Fetal death has been correlated with impaired secretion of some of these regulatory factors.

OBJECTIVE:

The aim of the present study was to evaluate, in placentas collected from fetal death, the gene expression of inflammatory, proliferative and protective factors. STUDY

DESIGN:

Cases of fetal death in singleton pregnancy were retrospectively selected, excluding pregnancies complicated by fetal anomalies, gestational diabetes, intrauterine growth restriction and moderate to severe maternal diseases. A group of placentas collected from healthy singleton term pregnancies were used as controls. Groups were compared regarding maternal and gestational age, fetal sex and birthweight. Placental messenger RNA expression of inflammatory (interleukin 6), proliferative (activin A, transforming growth factor ß1) and regulatory (vascular endothelial growth factor, vascular endothelial growth factor receptor 2, ATP-binding cassette transporters (ABC) ABCB1 and ABCG2, sphingosine 1-phosphate signaling pathway) markers was conducted using real-time polymerase chain reaction. Statistical analysis and graphical representation of the data were performed using the GraphPad Prism 5 software. For the statistical analysis, Student's t test was used, and P values<.05 were considered significant.

RESULTS:

Placental mRNA expression of interleukin 6 and vascular endothelial growth factor receptor 2 resulted significantly higher in the fetal death group compared to controls (P<.01), while activin A, ABCB1, and ABCG2 expression resulted significantly lower (P<.01). A significant alteration in the sphingosine 1-phosphate signaling pathway was found in the fetal death group, with an increased expression of the specific receptor isoforms sphingosine 1-phosphate receptor 1, 3, and 4 (sphingosine 1-phosphate1, sphingosine 1-phosphate3, sphingosine 1-phosphate4) and of sphingosine kinase 2, 1 of the enzyme isoforms responsible for sphingosine 1-phosphate synthesis (P<.01).

CONCLUSION:

The present study confirmed a significantly increased expression of placental interleukin 6 and vascular endothelial growth factor receptor 2 mRNA, and for the first time showed an increased expression of sphingosine 1-phosphate receptors and sphingosine kinase 2 as well as a decreased expression of activin A and of selected ATP-binding cassette transporters, suggesting that multiple inflammatory and protective factors are deranged in placenta of fetal death.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Am J Obstet Gynecol Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Am J Obstet Gynecol Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos