scholarly journals Increased expression of pentraxin 3 in placental tissues from patients with unexplained recurrent pregnancy loss

2019 ◽  
Vol 22 (1) ◽  
pp. 21-28 ◽  
Author(s):  
S Zeybek ◽  
E Tepeli ◽  
GO Cetin ◽  
V Caner ◽  
H Senol ◽  
...  

AbstractPentraxin 3 (PTX3), a prototypical member of the long pentraxin subfamily, is a evolutionarily conserved multimeric pattern recognition receptor involved in the humoral component of the innate immune system. Pentraxin 3 is released when tissue is stressed or damaged, and interacts with many different ligands. Pentraxin 3 exerts a pivotal role both as a regulator and as an indicator of inflammatory response in the pathogenesis of many diseases such as sepsis, vasculitis and preeclampsia. Uncontrolled inflammatory response is considered a major cause of unexplained recurrent pregnancy loss (URPL). We determined the PTX3 messenger ribonucleic acid (mRNA) and protein expression levels in placentai tissues from 50 women with URPL, and made comparison with those in 50 age-matched control subjects. In quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry analyses, PTX3 mRNA and protein levels, respectively, were significantly increased in URPL patients compared with their respective controls (p = 0.0001). Although no significant correlations were identified between PTX3 expression levels and clinical parameters such as maternal age, numbers of previous pregnancy losses, and gestational age at miscarriage, PTX3 mRNA expression was significantly higher in patients with no live births than in women with previous live births (p = 0.0001). Our study suggests that tissue-specific expression of PTX3 is associated with URPL. Further larger studies are required to determine whether PTX3 expression can be used as a biomarker to manage URPL in routine clinical practice.

Author(s):  
Yun Feng ◽  
Xueyin Li ◽  
Xi Chen ◽  
Mengling Zhao ◽  
Qian Wang ◽  
...  

IntroductionThe mechanisms underlying the pathogenesis of recurrent pregnancy loss (RPL) and the effective approaches to treat this disease still remain vague and absent. Proteinases of ADAMTS family play important roles in embryonic growth and development. Our previous study suggest a role of ADAMTS13 during pregnancy. Current Study was to determine the expression of ADAMTS13 in human endometrium and its association with RPL.Material and methodsThe spatiotemporal expression of ADAMTS13 in human endometrium was examined by immunohistochemistry. real-time PCR sand western blot were then employed to determine the mRNA and protein expression levels of ADAMTS13 in human endometrium. Proteolytic cleavage of FRETS-VWF73 were performed to determine the activity of ADAMTS13 in plasma and that secreted by human endometrium. ELISA was carried out to measure plasma VWF antigen.ResultsWe show that proteolytically active ADAMTS13 is expressed in human endometrium throughout the menstrual cycle and pregnancy. The decidual expression levels of mRNA and protein in women with RPL were significantly lower compared with women with uncomplicated pregnancies (P<0.01, P<0.05, respectively). Furthermore, significantly reduced plasma ADAMTS13 activity (median [range] 69.09 [65.2–93.7]% versus 93.62 [88.1–115.6]%, P<0.001) and elevated plasma VWF antigen levels (median [range] of 125.5 [54.2–262.8]% versus 91.9[80.4–138.7]%, P < 0.01) were detected in RPL patients compared with the control group.ConclusionsThese findings suggest that ADAMTS13 may play a role in embryo implantation and the pathogenesis of recurrent pregnancy loss. Further investigation on ADAMTS13 gene knockout animal models is necessary for understanding the molecular mechanisms of the biological roles of ADAMTS13 during gestation.


2020 ◽  
Vol 47 (1) ◽  
pp. 68-76
Author(s):  
Saeideh Hamidian ◽  
Ali Reza Talebi ◽  
Farzaneh Fesahat ◽  
Mohammad Bayat ◽  
Ali Mohammad Mirjalili ◽  
...  

Objective: Since sperm abnormalities are known to be a major reason for recurrent pregnancy loss (RPL), any defects in DNA structure and chromatin condensation can place embryos at risk in the early stage of development and implantation. As antioxidants such as vitamin C may play a protective role against the destruction of protamine genes in sperm chromatin, this study was conducted to evaluate the effects of vitamin C on chromatin and the expression of protamine genes in the male partners of couples with RPL.Methods: Twenty male partners of couples with RPL were selected as the intervention group and received vitamin C supplementation (250 mg daily for 3 months). Healthy fertile men (n=20) were included as controls. Sperm chromatin, DNA integrity, and the expression levels of protamine genes were evaluated before and after treatment.Results: Significant differences were found in sperm morphology, protamine deficiency, and apoptosis between the two groups and before and after vitamin C administration. A significant change was found in mRNA levels of <i>PRM1, PRM2</i>, and the <i>PRM1/PRM2</i> ratio after treatment.Conclusion: Daily oral administration of vitamin C may improve human sperm parameters and DNA integrity by increasing protamine gene expression levels in the male partners of couples with RPL. The beneficial effects of vitamin C supplementation as an antioxidant for the male partners of couples with RPL could lead to improved pregnancy outcomes in these cases.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yamnia I Cortes ◽  
Shuo Zhang ◽  
Diane C Berry ◽  
Jon Hussey

Introduction: Pregnancy loss, including miscarriage and stillbirth, affect 15-20% of pregnancies in the United States annually. Accumulating evidence suggests that pregnancy loss is associated with greater cardiovascular disease (CVD) burden later in life. However, associations between pregnancy loss and CVD risk factors in early adulthood (age<35 years) have not been assessed. Objective: To examine associations between pregnancy loss and CVD risk factors in early adulthood. Methods: We conducted a secondary data analysis using the public-use data set for Wave IV (2007-2009) of the National Longitudinal Study of Adolescent to Adult Health (Add Health). Our sample consisted of women, ages 24-32 years, with a previous pregnancy who completed biological data collection (n=2,968). Pregnancy loss was assessed as any history of miscarriage or stillbirth; and as none, one, or recurrent (≥2) pregnancy loss. Dependent variables included physical measures and blood specimens: body mass index (BMI), blood pressure, diabetes status, and dyslipidemia. Associations between pregnancy loss and each CVD risk factor were tested using linear (for BMI) and logistic regression adjusting for sociodemographic factors, parity, pre-pregnancy BMI, smoking during pregnancy, and depression. Results: Six hundred and ninety-three women (23%) reported a pregnancy loss, of which 21% reported recurrent pregnancy loss. Women with all live births were more likely to identify as non-Hispanic White (73%) and report a higher annual income. After adjusting for sociodemographics (age, race/ethnicity, education, income), pregnancy loss was associated with a greater BMI (ß=0.90; SE,0.39). In fully-adjusted models, women with recurrent pregnancy loss were more likely to have hypertension (AOR, 2.50; 95%CI, 1.04-5.96) and prediabetes (AOR, 1.93; 95%CI. 1.11-3.37) than women with all live births; the association was non-significant for women with one pregnancy loss. Conclusions: Pregnancy loss is associated with a more adverse CVD risk factor profile in early adulthood. Findings suggest the need for CVD risk assessment in young women with a prior pregnancy loss. Further research is necessary to identify underlying risk factors of pregnancy loss that may predispose women to CVD.


2019 ◽  
Author(s):  
Chitra Devi Ramachandran ◽  
Khadijeh Gholami ◽  
Sau-Kuen Lam ◽  
Mohd Rais Mustafa ◽  
See-Ziau Hoe

AbstractAn increase in blood pressure (BP) by a high-salt (HS) diet may involve the changes in the expression of epithelium sodium channels (ENaCs) and aquaporins (AQPs) in the kidney which affect the sodium- and water-handling mechanisms. In the present study, spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were exposed to HS and regular-salt (RS) diets for 6 weeks and fluid intake was monitored. After 6 weeks, mean arterial pressure (MAP) and plasma hormonal activity of atrial natriuretic peptide (ANP), levels of angiotensin II (Ang II), aldosterone and arginine vasopressin (AVP) were determined. The expression of mRNA and protein levels of ENaC and AQP subunits in kidneys were quantified by real-time PCR and Western blotting. High-salt diet caused higher MAP only in SHRs and higher fluid intake in both strains of rats when compared with their respective controls on RS diet. The plasma levels of Ang II and aldosterone were low in both SHRs and WKY rats fed with HS diet. Meanwhile, plasma ANP activity was high in both strains of rats on HS diet; whilst the AVP showed vice versa effects. The renal expression of mRNA and protein levels of α- and γ-ENaCs was lowered by HS diet in both SHRs and WKY rats. Although β-ENaC mRNA and protein expression levels were depressed in SHRs but they were enhanced in WKY rats. On the other hand, AQP-1, 2 and 7 mRNA and protein expression levels were lowered in both strains of rats fed with HS diet, while that of AQP-3, 4 and 6 showed no significant changes. The suppression of mRNA and protein expression levels of ENaC and AQP subunits suggests that the HS-induced increase in the MAP of SHRs may not be due to the renal sodium and water retention solely.


Reproduction ◽  
2020 ◽  
Vol 159 (4) ◽  
pp. R203-R211 ◽  
Author(s):  
Elizabeth Soczewski ◽  
Esteban Grasso ◽  
Lucila Gallino ◽  
Vanesa Hauk ◽  
Laura Fernández ◽  
...  

Decidualization denotes the reprogramming of endometrial stromal cells that includes the secretion of different mediators like cytokines, chemokines, and the selective recruitment of immune cells. This physiological process involves changes in the secretome of the endometrial stromal cells leading to the production of immunomodulatory factors. The increased amount of protein secretion is associated with a physiological endoplasmic reticulum (ER) stress and the resulting unfolded protein response (UPR), allowing the expansion of ER and the machinery to assist the protein folding. Notably, the signaling pathways involved in the ER stress and the UPR are interconnected with the onset of a sterile inflammatory response, as well as with angiogenesis. Both of these processes have a key role in decidualization and placentation, therefore, alterations in them could lead to pregnancy complications. In this review, we will discuss how the induction of ER stress and the UPR processes that accompanies the decidualization are associated with embryo implantation and whether they might condition pregnancy outcome. The ER stress activates/triggers sensing proteins which, among others, induces kinase/RNAse-TXNIP expression, activating the NLRP3 inflammasome. This multiprotein system allows caspase-1 activation, which catalyzes the cleavage of the inactive IL-1β proform toward the mature secretory form, with pro-implantatory effects. However, the sterile inflammatory response should be later controlled in favor of a tolerogenic microenvironment to sustain pregnancy. In accordance, alterations of the ER stress and UPR processes can be reflected in recurrent implantation failures (RIF), recurrent pregnancy loss (RPL), or complications associated with deficient placentation, such as preeclampsia (PE).


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Wen-cong Li ◽  
Su-xian Zhao ◽  
Wei-guang Ren ◽  
Hui-juan Du ◽  
Yu-guo Zhang ◽  
...  

The liver is the only visceral organ that exhibits a remarkable capability of regenerating in response to partial hepatectomy (PH) or chemical injury. Improving liver regeneration (LR) ability is the basis for the favourable treatment outcome of patients after PH, which can serve as a potential indicator for postoperative survival. The present study aimed to investigate the protective effects of Yiqi Huoxue recipe (YQHX) on LR after PH in rats and further elucidate its underlying mechanism. A two-thirds PH rat model was used in this study. Wistar rats were randomly divided into four groups: sham-operated, PH, YQHX + PH, and Fuzheng Huayu decoction (FZHY) + PH groups. All rats were sacrificed under anesthesia at 24 and 72 h after surgery. The rates of LR were calculated, and the expression levels of cyclin D1 and c-jun were determined by immunohistochemical staining. The protein levels of p-JNK1/2, JNK1/2, p-c-jun, c-jun, Bax, and Bcl-2 were detected by Western blotting, while the mRNA levels of JNK1, JNK2, c-jun, Bax, and Bcl-2 were examined by real-time polymerase chain reaction (RT-PCR). At the corresponding time points, YQHX and FZHY administration dramatically induced the protein levels of p-JNK1/2 compared to the PH group p<0.05, while FZHY + PH group showed prominently increase in p-JNK1/2 protein levels compared to the YQHX + PH group p<0.05. A similar trend was observed for the expression levels of p-c-jun. Compared to the PH group, YQHX and FZHY markedly reduced the mRNA and protein expression levels of Bax at 24 h after PH, while those in the FZHY + PH group decreased more obviously p<0.05. Besides, in comparison with the PH group, YQHX and FZHY administration predominantly upregulated the mRNA and protein expression levels of Bcl-2 at 24 and 72 h after PH p<0.05. In conclusion, YQHX improves LR in rats after PH by inhibiting hepatocyte apoptosis via the JNK signaling pathway.


2021 ◽  
Author(s):  
Mina Tutunfroush ◽  
Saeid Ghorbian ◽  
Jafar Mohseni ◽  
Shahla Danaii

Abstract Recently, circulating microRNAs have attracted much attention because they can serve as reliable non-invasive diagnostic and prognostic biomarkers for pregnancy-related complications. So, this study aimed to quantify miR-23a-3p, miR-101-3p and miR-let-7c expression levels in plasma of patients with idiopathic recurrent pregnancy loss (iRPL) and healthy subjects and to evaluate their potential diagnostic value in iRPL patients. A total of 120 plasma samples were obtained from sixty women with a history of at least two consecutive iRPL and sixty healthy women without a history of miscarriage to evaluate the expression levels of the circulating miR-23a-3p, miR-101-3p and miR-let-7c by quantitative real-time polymerase chain reaction (qPCR) technique. The correlation between studied miRNAs and clinicopathological parameters was also assessed. Receiver operating characteristic (ROC) curve was plotted to determine the diagnostic accuracy of miR-23a-3p, miR-101-3p and miR-let-7c in iRPL. Our results showed that the miR-23a-3p expression level in plasma of iRPL patients was lower than those in healthy controls but without a statistically significant difference (P = 0.113). The expression levels of miR-101-3p and miR-let-7c were significantly downregulated in iRPL patients compared with healthy subjects (P < 0.05). The expression levels of miR-23a-3p and miR-let-7c was negatively correlated with number of abortions in iRPL patients. We observed statistically significant positive correlation between miR-23a-3p and miR-101-3p (r = 0.478, P = 0.001), miR-23a-3p and miR-let-7c (r = 0.561, P = 0.0001), miR-101-3p and miR-let-7c (r = 0.533, P = 0.0001) in patients with iRPL. The current study provides evidence indicating that downregulation of miR-23a-3p, miR-101-3p and miR-let-7c may be associated with iRPL.


2021 ◽  
Author(s):  
Jia Wang ◽  
Meijuan Sun ◽  
Wenlong Du ◽  
Yuanxian Guo ◽  
Jiebin Pan ◽  
...  

Abstract Background Studies have shown that pyruvate kinase M2 (PKM2) and Notch1 are highly expressed in colorectal cancer (CRC) tissues and have a certain relationship with disease occurrence and development. The expression levels of PKM2 and Notch1 are also related to the effect of chemotherapy and radiotherapy, which seriously influence the prognosis of CRC patients. Thus, both PKM2 and Notch1 have been identified as key targets of CRC treatment and research. However, correlations between PKM2 and Notch1 have not yet been established. Methods Immunohistochemical analysis was conducted to detect the expression of PKM2 and Notch1 in CRC tissues. The mRNA and protein expression levels of PKM2 and Notch1 in CRC cell lines were detected by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR) and western blot analysis, respectively. Compound 3K and tangeretin (TGN) were used to inhibit the expression of PKM2 and Notch1, respectively. The proliferation and migration of cancer cells in each group were detected with the CCK-8 and wound healing assays. Results The Immunohistochemical analysis showed that PKM2 and Notch1 were highly expressed in CRC and related to tumor stage and lymph node metastasis. The qRTPCR and western blot results showed that PKM2 and Notch1 were notably upregulated in CRC cells both at the mRNA and protein levels. PKM2 and Notch1 form a positive feedback loop to promote the occurrence and development of CRC, and inhibition of PKM2 and Notch1 has a synergistic effect on the proliferative and invasive capabilities of CRC cells. Conclusion The combination of the PKM2 inhibitor compound 3K and the Notch1 inhibitor TGN presents a novel and effective strategy for treatment of CRC.


2018 ◽  
Author(s):  
Mark J. Hickman ◽  
Andrea Jackson ◽  
Abigail Smith ◽  
Julianne Thornton ◽  
Amanda Tursi

ABSTRACTIt is not understood what evolutionary factors drive some genes to be expressed at a higher level than others. Here, we hypothesized that a gene’s function plays an important role in setting expression level. First, we established that eachS. cerevisiaegene is maintained at a specific expression level by analyzing RNA-seq data from multiple studies. Next, we found that mRNA and protein levels were maintained for the orthologous genes inS. pombe, showing that gene function, conserved in orthologs, is important in setting expression level. To further explore the role of gene function in setting expression level, we analyzed mRNA and protein levels ofS. cerevisiaegenes within gene ontology (GO) categories. The GO framework systematically defines gene function based on experimental evidence. We found that several GO categories contain genes with statistically significant expression extremes; for example, genes involved in translation or energy production are highly expressed while genes involved in chromosomal activities, such as replication and transcription, are weakly expressed. Finally, we were able to predict expression levels using GO information alone. We created and optimized a linear equation that predicted a gene’s expression based on the gene’s membership in 161 GO categories. The greater number of GO categories with which a gene is associated, the more accurately expression could be predicted. Taken together, our analysis systematically demonstrates that gene function is an important determinant of expression level.


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