CD39 downregulation in chronic intervillositis of unknown etiology

  • Yuichiro SatoEmail author
  • Kazunari Maekawa
  • Murasaki Aman
  • Atushi Yamashita
  • Yuki Kodama
  • Yohei Maki
  • Hiroshi Sameshima
  • Yujiro Asada
Original Article


Chronic intervillositis of unknown etiology (CIUE) is a rare placental lesion associated with infiltration of mononuclear inflammatory cells into the intervillous space, poor perinatal outcomes (intrauterine fetal demise or fetal growth restriction), and high rates of recurrence. CD39 is the ectonucleotidase that protects tissues from inflammatory stress and cell injury, which is localized on the surface of villi in normal placentas; however, its expression and role in CIUE are unknown. The aims of this retrospective study were to determine the expression of CD39 in CIUE and its significance in pregnancy outcomes. We compared the number of CD68- and CD3-positive cells, CD39 expression, and complement 4d (C4d) and fibrin deposition in placental tissues from patients with CIUE (n = 22) and gestational age-matched controls (n = 20), and between CIUE pregnancies with poor and good outcomes. The numbers of CD68- or CD3-positive cells were significantly higher (P < 0.0001), whereas CD39 expression on the surface of villi and endothelial cells of the stem villi was significantly lower in the CIUE group than that in controls (45% vs. 95%, P < 0.0001 and 77% vs. 96%, P < 0.001, respectively). C4d and fibrin deposition were also significantly increased in CIUE compared with those of controls. Furthermore, CD39 downregulation and the number of CD68 cells were strongly associated with poor pregnancy outcomes (P < 0.01 and P < 0.05, respectively), but other histological parameters (CD3, C4d, and fibrin) did not show this association. Our study suggests that CD39 downregulation is a useful marker of CIUE and is associated with poor pregnancy outcomes in patients with CIUE.


Chronic intervillositis of unknown etiology CD39 CD68 CD3 C4d Abortion Fetal growth restriction 



We thank Ritsuko Sotomura and Takako Tokumitsu for their assistance with immunohistochemical staining. We would also like to thank Editage ( for English language editing.

Author contributions

YS, KM, and MA conceived and designed the study and wrote the manuscript. AY, YS, YK, and YM collected and analyzed the data. HS and YA wrote, edited, and reviewed the manuscript. All authors participated in the interpretation of the results and writing of the report and approved the final version submitted. YS takes full responsibility for the work, as a whole, including the study design, access to data, and the decision to submit and publish the manuscript.


This study was partly supported by Grants-in-Aid for Scientific Research in Japan (No. 19K07417) from the Ministry of Education, Culture, Sports, Science and Technology, and a Grant-in-Aid for clinical research from Miyazaki University Hospital.

Compliance with ethical standards

This study was approved by the Medical Ethics Committee of the Faculty of Medicine at the University of Miyazaki on September 4, 2018 (project number 0-0401).

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Diagnostic Pathology, Faculty of Medicine, Miyazaki University HospitalUniversity of MiyazakiMiyazakiJapan
  2. 2.Department of Pathology, Faculty of MedicineUniversity of MiyazakiMiyazakiJapan
  3. 3.Department of Obstetrics and Gynecology, Faculty of MedicineUniversity of MiyazakiMiyazakiJapan

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