Article Text

Download PDFPDF
Concise report
Severe fibrotic changes and altered expression of angiogenic factors in maternal scleroderma: placental findings
  1. L Ibba-Manneschi1,
  2. M Manetti1,2,
  3. A F Milia2,
  4. I Miniati2,
  5. G Benelli1,
  6. S Guiducci2,
  7. F Mecacci3,
  8. G Mello3,
  9. S Di Lollo4,
  10. M Matucci-Cerinic2
  1. 1
    Department of Anatomy, Histology and Forensic Medicine, University of Florence, Florence, Italy
  2. 2
    Department of Biomedicine, Division of Rheumatology, AOUC, and Excellence Centre for Research, Transfer and High Education DENOthe, University of Florence, Florence, Italy
  3. 3
    Department of Gynecology, Perinatology and Human Reproduction, University of Florence, Florence, Italy
  4. 4
    Department of Human Pathology and Oncology, University of Florence, Florence, Italy
  1. Correspondence to Professor L Ibba-Manneschi, Department of Anatomy, Histology and Forensic Medicine, University of Florence, Viale G B Morgagni 85, 50134, Florence, Italy; ibba{at}


Objective: Pregnant women with systemic sclerosis (SSc; scleroderma) have an increased risk of premature delivery and small full-term infants. During placental development, angiogenesis and vascular remodelling are essential for a successful pregnancy outcome. An analysis was made of the pathological changes and expression of angiogenic factors in SSc placentas.

Methods: Placenta biopsies were obtained from three patients with SSc and four healthy uncomplicated pregnancies after delivery at 34–38 weeks of gestation. The sections were stained with Masson’s trichrome and phosphotungstic-acid-haematoxylin and immunostained for connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), vascular endothelial growth factor (VEGF), placenta growth factor (PlGF) and receptors VEGFR-1 and VEGFR-2.

Results: The pathological findings were signs of decidual vasculopathy, increased syncytiotrophoblast knotting, placental infarcts and villous hypoplasia. Severe and diffuse perivascular and stromal fibrosis of decidua and chorionic villi, and extensive deposition of fibrinoid material around decidual vessels and in intervillous spaces were observed. Strong CTGF expression in the vessel wall, decidual cells and fibroblasts and α-SMA+ myofibroblasts were found. VEGF and VEGFR-2 expression was stronger in SSc than in healthy placentas, while VEGFR-1 expression was similar to controls. PlGF immunopositivity was weaker in SSc.

Conclusion: In SSc placentas, severe fibrosis and abnormal vascular remodelling were detected. This may result in reduced blood flow leading to deep sufferance of maternal placenta and possible premature delivery.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • ▸ Additional details are published online only at

  • Funding This study was supported by grants from the Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR), and the Associazione per lo studio della Sclerosi Sistemica e delle Malattie Fibrosanti (ASSMaF onlus).

  • Competing interests None.

  • Provenance and Peer review Not commissioned; externally peer reviewed.