Haidy El-Azzamy, Andrea Balogh, Roberto Romero, Yi Xu, Christopher LaJeunesse, Olesya Plazyo, Zhonghui Xu, Theodore G. Price, Zhong Dong, Adi L. Tarca, Zoltan Papp, Sonia S. Hassan, Tinnakorn Chaiworapongsa, Chong Jai Kim, Nardhy Gomez-Lopez, Nandor Gabor Than
J Pathol Transl Med. 2017;51(3):264-283. Published online February 22, 2017
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.
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BACKGROUND Galectin-3 and galectin-7 may play roles in human carcinogenesis. The aim of this study was to investigate the expressions of galectin-3 and galectin-7 in gastric dysplasia and adenocarcinoma. METHODS: We examined the expressions of galectin-3, galectin-7, and P53 in nonneoplastic gastric mucosa, gastric epithelial dysplasia (GED), and adenocarcinoma by immunohistochemistry. Twenty cases of nonneoplastic gastric mucosa, 20 cases of low grade GED, 20 cases of high grade GED, 40 cases of early gastric cancer (EGC), and 60 cases of advanced gastric cancer (AGC) are included for study. RESULTS: In the nonneoplastic tissue, only galectin-3 was expressed in the intestinal metaplasia. Galectin-7 was not stained in the nonneoplastic gastric mucosa. Galectin-3 was expressed in 3 cases of low grade GED (15%), 13 cases of high grade GED (65%), 2 cases of EGC (5%), and 5 cases of AGC (8%), respectively.
Galectin-7 was expressed in 2 cases of low grade GED (10%), 3 cases of high grade GED (15%), and 4 cases of EGC (10%), respectively. However, it was not expressed in AGC. CONCLUSIONS Based on our results, the expressions of galectin-3 and galectin-7 may contribute to the development of gastric epithelial dysplasia and early gastric cancer, rather than contributing to the progression of gastric adenocarcinoma.