Journal of Pathology and Translational Medicine

Original Articles

Characteristic Changes in Decidual Gene Expression Signature in Spontaneous Term Parturition: 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; DOI: https://doi.org/10.4132/jptm.2016.12.20

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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.

Citations

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Zhi Lin, Jia-Lu Shi, Min Chen, Zi-Meng Zheng, Ming-Qing Li, Jun Shao
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Proteomic profile of extracellular vesicles in maternal plasma of women with fetal death
Dahiana M. Gallo, Wendy Fitzgerald, Roberto Romero, Nardhy Gomez-Lopez, Dereje W. Gudicha, Nándor Gábor Than, Mariachiara Bosco, Tinnakorn Chaiworapongsa, Eunjung Jung, Arun Meyyazhagan, Manaphat Suksai, Francesca Gotsch, Offer Erez, Adi L. Tarca, Leonid
The Journal of Maternal-Fetal & Neonatal Medicine.2023;[Epub] CrossRef
Downregulated INHBB in endometrial tissue of recurrent implantation failure patients impeded decidualization through the ADCY1/cAMP signalling pathway
Hui Zhang, Zhilong Wang, Quan Zhou, Zhiwen Cao, Yue Jiang, Manlin Xu, Jingyu Liu, Jidong Zhou, Guijun Yan, Haixiang Sun
Journal of Assisted Reproduction and Genetics.2023; 40(5): 1135. CrossRef
Regulation of inflammatory genes in decidual cells: Involvement of the bromodomain and extra-terminal family proteins
Sandeep Ajgaonkar, Jonathan J. Hirst, Mary Norris, Tamas Zakar, Giovanni Camussi
PLOS ONE.2023; 18(3): e0280645. CrossRef
Decidual cells and decidualization in the carnivoran endotheliochorial placenta
Mónica Elizabeth Diessler, Rocío Hernández, Gimena Gomez Castro, Claudio Gustavo Barbeito
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Galectin-1 and Galectin-9 Concentration in Maternal Serum: Implications in Pregnancies Complicated with Preterm Prelabor Rupture of Membranes
Dorota Grażyna Boroń, Aleksy Świetlicki, Michał Potograbski, Grażyna Kurzawińska, Przemysław Wirstlein, Daniel Boroń, Krzysztof Drews, Agnieszka Seremak-Mrozikiewicz
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Do Helper T Cell Subtypes in Lymphocytic Thyroiditis Play a Role in the Antitumor Effect?: Seok Woo Yang, Seong-Ho Kang, Kyung Rae Kim, In Hong Choi, Hang Seok Chang, Young Lyun Oh, Soon Won Hong; J Pathol Transl Med. 2016;50(5):377-384. Published online September 15, 2016; DOI: https://doi.org/10.4132/jptm.2016.07.25

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Abstract PDF

Background
Papillary thyroid carcinoma (PTC) is frequently accompanied by lymphocytic thyroiditis (LT). Some reports claim that Hashimoto’s thyroiditis (the clinical form of LT) enhances the likelihood of PTC; however, others suggest that LT has antitumor activity. This study was aimed to find out the relationship between the patterns of helper T cell (Th) cytokines in thyroid tissue of PTC with or without LT and the clinicopathological manifestation of PTC.
Methods
Fresh surgical samples of PTC with (13 cases) or without (10 cases) LT were used. The prognostic parameters (tumor size, extra-thyroidal extension of PTC, and lymph node metastasis) were analyzed. The mRNA levels of two subtypes of Th cytokines, Th1 (tumor necrosis factor α [TNF-α], interferon γ [IFN-γ ], and interleukin [IL] 2) and Th2 (IL-4 and IL-10), were analyzed. Because most PTC cases were microcarcinomas and recent cases without clinical follow-up, negative or faint p27 immunoreactivity was used as a surrogate marker for lymph node metastasis.
Results
PTC with LT cases showed significantly higher expression of TNF-α (p = .043), IFN-γ (p < .010), IL-4 (p = .015) than those without LT cases. Although the data were not statistically significant, all analyzed cytokines (except for IL-4) were highly expressed in the cases with higher expression of p27 surrogate marker.
Conclusions
These results indicate that mixed Th1 (TNF-α, IFN-γ , and IL-2) and Th2 (IL-10) immunity might play a role in the antitumor effect in terms of lymph node metastasis.

Citations

Citations to this article as recorded by

Obesity and Thyroid Cancer Risk: An Update
Fabiana Franchini, Giuseppe Palatucci, Annamaria Colao, Paola Ungaro, Paolo Emidio Macchia, Immacolata Cristina Nettore
International Journal of Environmental Research and Public Health.2022; 19(3): 1116. CrossRef
Association between Hashimoto thyroiditis and clinical outcomes of papillary thyroid carcinoma: A meta-analysis
Qizhi Tang, Weiyu Pan, Liangyue Peng, Francis Moore
PLOS ONE.2022; 17(6): e0269995. CrossRef
The Heat Shock Protein Story—From Taking mTORC1,2 and Heat Shock Protein Inhibitors as Therapeutic Measures for Treating Cancers to Development of Cancer Vaccines
Peter Chin Wan Fung, Regina Kit Chee Kong
Journal of Cancer Therapy.2017; 08(11): 962. CrossRef

Cytokine Expression on Microglial Proliferation and Apoptosis in Rat Lumbar Spinal Cord Following Unilateral Sciatic Nerve Transection.: Sang Pyo Kim, Seung Il Suh, Young Rok Cho, Seung Che Cho, Seung Pil Kim, Jong Wook Park, Jyung Sik Kwak; Korean J Pathol. 1998;32(2):94-103.

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Abstract PDF: This study was carried out to elucidate the cytokine mRNAs expression and morphological features according to a microglial proliferation and apoptosis in a rat lumbar spinal cord, after a right sciatic nerve transection. The control group was composed of 5 rats (Spraque-Dawley) and the experimental group was composed of 70 rats. On post operation day (pod) 1, 2, 3, 5, and 7 eight rats were sacrificed on those days. On pod 10 five rats were sacrificed as well as five rats sacrificed on post operation weeks 2, 3, 4, 5, and 6. On light microscopy, activated microglia were often found in a perineuronal position around motoneurons in the ventral gray matter and more randomly distributed throughout the neuropil in the dorsal gray matter of lumbar spinal cord. GSA I-B4-positive microglia began to increase from 1 day after transection, and reached peak at 2~3 days and it persisted at 5~7 days and decreased thereafter. TUNEL-positive microglia was not observed in control group and began to increase from 5 days after transection and increased gradually until 3 weeks and decreased thereafter. On in situ RT-PCR, the positive signal for IL-1alpha and IL-6 mRNA was found mainly in the cytoplasm of the activated microglia and astrocytes at 1 day after transection and showed stronger signal at 3 days and decreased gradually until 10 days. TNF-alpha mRNA was detected 1 day after transection and remained for 7 days and localized to activated microglia as well as probably some astrocytes. The signal intensity of IL-1alpha and IL-6 mRNA was generally stronger than TNF-alpha mRNA. On transmission electron microscopy, there were chromatin condensation with margination toward nuclear membrane and condensation of cytoplasm at 3 days after transection. Apoptotic bodies were found after 5 days and increased gradually until 3 weeks. According to the above findings, it is concluded that apoptosis appears to be one mechanism by which activated microglia are gradually eliminated and cytokine expression seems to played an active role in the microglial turnover.

Intrauterine Infection as a Cause of the Neonatal Pulmonary Injury and Bronchopulmonary Dysplasia.: Jin Haeng Chung, Jeong Wook Seo; Korean J Pathol. 2000;34(6):431-436.

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Abstract PDF: The pathogenetic role of intrauterine infection to the neonatal pulmonary injury and bronchopulmonary dysplasia was assessed by studying the interleukin-6 (IL-6) level in the umbilical cord blood and the early morphologic changes of the neonatal lung. Patients were grouped into bronchopulmonary dysplasia (4 cases), chorioamnionitis without chronic lung injury (4 cases), and 6 cases without morphologic evidence of chronic lung injury or placental inflammation. IL-6 level of umbilical cord blood was higher in babies with bronchopulmonary dysplasia (17.7 pg/ml) compared to those with chorioamnionitis (4.7 pg/ml) or those with morphologically normal lung and placenta (6.2 pg/ml). Morphologic parameters of neonatal pulmonary injury were hyaline membrane, terminal bronchiole inflammation, terminal bronchiole regeneration, alveolar collapse and fibroblastic proliferation. Bronchiolar regeneration was the most peculiar feature seen in the lung with bronchopulmonary dysplasia. Alveolar collapse and interstitial fibroblastic reaction were commonly seen in bronchopulmonary dysplasia. The postnatal age at death was higher in those with bronchopulmonary dysplasia, although the occurrence of the morphologic changes was related with the chronicity of those lesions. These findings suggest that intrauterine infection is an aggravating factor for the neonatal pulmonary injury and bronchopulmonary dysplasia, although the early stage of the lung injury is not a definitive indicator for the progressive pulmonary damage leading to the bronchopulmonary dysplasia.

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