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doi: https://doi.org/10.4132/jptm.2016.12.20    [Epub ahead of print]
Characteristic Changes in Decidual Gene Expression Signature in Spontaneous Term Parturition
Haidy El-Azzamy1,*, Andrea Balogh1,2,*, Roberto Romero1,3,4,5, Yi Xu1, Christopher LaJeunesse1, Olesya Plazyo1, Zhonghui Xu1, Theodore G. Price1, Zhong Dong1, Adi L. Tarca1,6, Zoltan Papp7, Sonia S. Hassan1,6, Tinnakorn Chaiworapongsa1,6, Chong Jai Kim1,8,9, Nardhy Gomez-Lopez1,6, Nandor Gabor Than1,6,7,10,11
1Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, and Detroit, MI, USA
2Department of Immunology, Eotvos Lorand University, Budapest, Hungary
3Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA
4Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA
5Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA
6Department of Obstetrics and Gynecology, Wayne State University, School of Medicine, Detroit, MI, USA
7Maternity Private Department, Kutvolgyi Clinical Block, Semmelweis University, Budapest, Hungary
8Department of Pathology, Wayne State University, School of Medicine, Detroit, MI, USA
9Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
10Systems Biology of Reproduction Lendulet Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary
11First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
Corresponding Author: Nandor Gabor Than ,Tel: +36-1-382-6788, Email: than.gabor@ttk.mta.hu
Received: October 2, 2016;  Revised: December 3, 2016  Accepted: December 20, 2016.  Published online: February 22, 2017.
ABSTRACT
Background:
The decidua has been implicated in the “terminal pathway” of human term parturition, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. However, the transcriptomic changes in the decidua leading to terminal pathway activation have not been systematically explored. This study aimed to compare the decidual expression of developmental signaling and inflammation-related genes before and after spontaneous term labor in order to reveal their involvement in this process.
Methods:
Chorioamniotic membranes were obtained from normal pregnant women who delivered at term with spontaneous labor (TIL, n=14) or without labor (TNL, n=15). Decidual cells were isolated from snap-frozen chorioamniotic membranes with laser microdissection. The expression of 46 genes involved in decidual development, sex steroid and prostaglandin signaling, as well as pro- and anti-inflammatory pathways was analyzed using high-throughput quantitative real-time polymerase chain reaction (qRT-PCR). Chorioamniotic membrane sections were immunostained and then semi-quantified for five proteins, and immunoassays for three chemokines were performed on maternal plasma samples.
Results:
The genes with the highest expression in the decidua at term gestation included insulin-like growth factor-binding protein 1 (IGFBP1), galectin-1 (LGALS1), and progestogen-associated endometrial protein (PAEP); the expression of estrogen receptor 1 (ESR1), homeobox A11 (HOXA11), interleukin 1β (IL1B), IL8, progesterone receptor membrane component 2 (PGRMC2), and prostaglandin E synthase (PTGES) was higher in TIL than in TNL cases; the expression of chemokine C-C motif ligand 2 (CCL2), CCL5, LGALS1, LGALS3, and PAEP was lower in TIL than in TNL cases; immunostaining confirmed qRT-PCR data for IL-8, CCL2, galectin-1, galectin-3, and PAEP; and no correlations between the decidual gene expression and the maternal plasma protein concentrations of CCL2, CCL5, and IL-8 were found.
Conclusions:
Our data suggests that with the initiation of parturition, the decidual expression of anti-inflammatory mediators decreases, while the expression of pro-inflammatory mediators and steroid receptors increases. This shift may affect downstream signaling pathways that can lead to parturition.
Key Words: Chemokines; Cytokines; Estrogens; Galectins; Leukocytes; Progesterone
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