Expression of interleukin-22 in decidua of patients with early pregnancy and unexplained recurrent pregnancy loss

  • Candice O’Hern Perfetto
  • Xiujun Fan
  • Sabita Dahl
  • Sacha Krieg
  • Lynn Marie Westphal
  • Ruth Bunker Lathi
  • Nihar R. Nayak
Reproductive Physiology and Disease



Researchers have hypothesized that an imbalance of immune cells in the uterine decidua and a dysfunction in cytokines they produce may contribute to recurrent pregnancy loss (RPL). The objective of this study was to determine if IL-22, IL-23 and IL-17 are expressed abnormally in the decidua of patients with RPL compared to those women with a normal pregnancy. We also sought to confirm that uterine natural killer (uNK) cells are lower in the decidua of patients with RPL, as well as identify IL-22 expression by uNK cells.


After meeting strict inclusion criteria, maternal decidua of nine patients with unexplained RPL and a confirmed euploid fetal loss, and 11 gestational age-matched patients undergoing elective pregnancy termination were included in our analysis. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to quantify RNA expression, Western blot was performed to quantify protein expression and immunohistochemistry (IHC) was performed to identify IL-22 and uNK cells.


We found that women with unexplained RPL and a euploid fetal loss had significantly less gene and protein expression of IL-22 in the decidua. Additionally, we found that IL-22 is primarily expressed by uNK cells in the decidua.


In conclusion, our results suggest that lower levels of IL-22 in the uterine decidua in patients with unexplained RPL may contribute to a disruption of decidual homeostasis and ultimately lead to early pregnancy loss.


Recurrent pregnancy loss Interleukin-22 Interleukin-17 Interleukin-23 Uterine decidua 



This research was made possible through the support of the Ernest and Amelia Gallo Endowed Postdoctoral fellowship, the Child Health Research Institute, Lucile Packard Foundation for Children’s Health, as well as the Stanford CTSA (grant number UL1 TR000093).

Conflict of interest

There are no known conflicts of interest associated with this publication.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Candice O’Hern Perfetto
    • 1
  • Xiujun Fan
    • 1
  • Sabita Dahl
    • 1
  • Sacha Krieg
    • 1
  • Lynn Marie Westphal
    • 1
  • Ruth Bunker Lathi
    • 1
  • Nihar R. Nayak
    • 1
  1. 1.Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and GynecologyStanford University Medical CenterPalo AltoUSA

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