The Liver X Receptor in Correlation with Other Nuclear Receptors in Spontaneous and Recurrent Abortions

Knabl, Julia; Pestka, Aurelia; Hüttenbrenner, Rebecca; Plösch, Torsten; Ensenauer, Regina; Welbergen, Lena; Hutter, Stefan; Günthner-Biller, Maria; Jeschke, Udo

doi:10.1155/2013/575604

Cited by 13 publications

(10 citation statements)

References 25 publications

(27 reference statements)

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“…Specimens were dehydrated in an ascending alcohol gradient and cover slipped with Eukitt ® quick hardening mounting medium (Sigma Aldrich, St. Louis, Missouri; USA). Positive control (human colon tissue) as well as negative control staining was carried out as described previously [10,37]. All slides were analyzed using the microscope Leitz Wetzlar (Germany; Type 307-148.001 514686).…”

Section: Immunohistochemistrymentioning

confidence: 99%

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PPARgamma Expression is Diminished in Macrophages of Recurrent Miscarriage Placentas

Kolben¹,

Rogatsch²,

Vattai³

et al. 2018

Preprint

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PPAR belongs to the group of nuclear receptors which is expressed in the trophoblast and together with other factors is responsible for the maintenance of pregnancy. Apart from that PPAR is also a main factor for macrophage polarization. The aim of this study was to investigate the combined expression pattern and frequency of PPAR under physiological circumstances and in spontaneous and recurrent miscarriages in the trophoblast and in maternal macrophages of the decidua. Human placental tissues of the first trimester (15 physiologic pregnancies, 15 spontaneous abortion & 16 recurrent miscarriage placentas) were analyzed for expression of the nuclear receptor PPAR. Expression changes were evaluated by immunohistochemistry and RT-PCR in trophoblast and in maternal macrophages of the decidua. Maternal macrophages were identified by double immunofluorescence using CD68 as marker for macrophages. The intermediate villous trophoblast revealed a significantly lower PPAR expression in spontaneous and recurrent abortion. Maternal macrophages express PPAR. Their number is significantly enhanced in the decidua of spontaneous miscarriages whereas in recurrent miscarriages maternal macrophages seem to express PPAR only in very few cases. PPAR is associated with an M2 polarization state that is common for decidual macrophages. The lack of PPAR in recurrent miscarriage decidual macrophages seems to be associated with a specific inflammatory response against the fetus.

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Section: Immunohistochemistrymentioning

confidence: 99%

“…Heterodimer partners are e.g. peroxisome proliferatoractivated receptor (PPAR), thyroid hormone receptor (TR), and liver X receptor (LXR) [2,[10][11][12]. Especially the expression of the isoform PPAR is linked to trophoblast invasion [13] and downregulation of the isoform RXRα seems to protect from apoptosis in human trophoblasts [9].…”

Section: Introductionmentioning

confidence: 99%

PPARgamma Expression is Diminished in Macrophages of Recurrent Miscarriage Placentas

Kolben¹,

Rogatsch²,

Vattai³

et al. 2018

Preprint

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“…11,12 These nuclear receptors are crucially involved in maintaining a viable pregnancy, their role had been clarified especially in human trophoblastic tissue: Toth et al showed that extravillous trophoblast (EVT) in placentas of miscarriages show a significantly higher expression of RXRα in comparison to EVT in placentas of elective termination of healthy pregnancies. 13 Recent studies showed that LXR expression is decreased in miscarriage 14 and PPARγ is increased in EVT of abortive tissue. 15 …”

Section: Introductionmentioning

confidence: 99%

RXRα is upregulated in first trimester endometrial glands of spontaneous abortions unlike LXR and PPARγ

et al. 2016

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Nuclear receptors are necessary for uterine invasion of the trophoblast and therefore important for maintaining a viable pregnancy. The aim of this study was to investigate the expression pattern and frequency of LXR, PPARγ and RXRα under physiological circumstances and in spontaneous abortions in endometrial glands and decidual tissue cells. A total of 28 (14 physiologic pregnancies/14 spontaneous abortion) human pregnancies in first trimester were analyzed for expression of the nuclear receptors LXR, RXRα and PPARγ. Expression changes were evaluated by immunohistochemistry in decidual tissue and endometrial glands of the decidua. RXRα expression was up-regulated in the endometrial glands of spontaneous abortion (P<0.015). Similar up regulation of RXRα was found in decidual tissue (P<0.05). LXR and PPARγ expression was unchanged in spontaneous abortion. By Correlation analysis we found a trend to positive correlation of LXR and PPARγ (Spearman correlation coefficient r=0.56, P=0.07) in endometrial glands. In decidual tissue, we found significant negative correlation in the control group, for the combination of RXRα and PPARγ (Spearman correlation coefficient r=0.913, P=0.03). Our data show that RXRα expression is increased in miscarriage in endometrial glands and correlation analysis showed that negative correlation between RXRα and PPARγ disappears in miscarriage. This shift is supposable responsible for the loss of regular function in trophoblast and embryonic tissue.

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“…1) 26 . Negative controls were performed by replacement of the primary antibodies by species specific isotype control antibodies (Dako) as described previously 27 . In addition, the IgG negative control was performed with unspecific isotype control IgG antibodies in Supplementary Fig.…”

Section: Methodsmentioning

confidence: 99%

The prostaglandin receptor EP2 determines prognosis in EP3-negative and galectin-3-high cervical cancer cases

Dietlmeier

Yao

Kühn

et al. 2020

Sci Rep

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Recently our study identified EP3 receptor and galectin-3 as prognosticators of cervical cancer. The aim of the present study was the analysis of EP2 as a novel marker and its association to EP3, galectin-3, clinical pathological parameters and the overall survival rate of cervical cancer patients. Cervical cancer tissues (n = 250), as also used in our previous study, were stained with anti-EP2 antibodies employing a standardized immunohistochemistry protocol. Staining results were analyzed by the iRS scores and evaluated for its association with clinical-pathological parameters. H-test of EP2 percent-score showed significantly different expression in FIGO I-IV stages and tumor stages. Kaplan-Meier survival analyses indicated that EP3-negative/EP2-high staining patients (EP2 IRS score ≥2) had a significantly higher survival rate than the EP3-negative/EP2-low staining cases (p = 0.049). In the subgroup of high galectin-3 expressing patients, the group with high EP2 levels (IRS ≥2) had significantly better survival rates compared to EP2-low expressing group (IRS <2, p = 0.044). We demonstrated that the EP2 receptor is a prognostic factor for the overall survival in the subgroup of negative EP3 and high galectin-3 expressed cervical cancer patients. EP2 in combination with EP3 or galectin-3 might act as prognostic indicators of cervical cancer. EP2, EP3, and galectin-3 could be targeted for clinical diagnosis or endocrine treatment in cervical cancer patients, which demands future investigations.Cervical cancer is the fourth most common female cancer type worldwide with nearly half a million new cases annually. 83% of all cases occur in developing countries, whereas in developed countries only 3.6% of new cancer cases are cervical cancer 1 . One of the main risk factors for cervical cancer is a persistent infection with specific Human Papillomavirus (HPV), the high-risk papillomavirus (HR-HPV) 2 . HPV is manifested in nearly 99.7% of all cervical cancer patients 3 . Belonging to the papillomavirus family, HPV is a non-enveloped, small, double-stranded DNA virus 3-5 . More than 200 HPV genotypes have been characterized worldwide 6 . The sub-classification in high-risk and low-risk is important for the HPV infections of the genital tract 5 . Low-risk subtypes, such as HPV-6, HPV-11, HPV-26, HPV-40, HPV-42, are the cause of genital warts and non-malignant lesions 2,5 , whereas high-risk HPV types like HPV-16 and HPV-18 were identified in cervical and other anogenital cancers 2,5 .Tumor cell differentiation, apoptosis, and oncogenesis are associated with prostanoids, including prostaglandin E 2 (PGE 2 ), prostaglandin D 2 (PGD 2 ), prostaglandin I 2 (PGI 2 ), prostaglandin F 2 (PGF 2 ) and thromboxane A 2 7 . Prostaglandins are important for tumor progression and tumor-associated angiogenesis as Amano et al. described 8 . PGE 2 signaling is well-known for apoptosis inhibition, angiogenesis, metastatic formation, and tumor progression. The membrane-bound EP receptors specific for PGE 2 are G-protein coupled receptors and...

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The Liver X Receptor in Correlation with Other Nuclear Receptors in Spontaneous and Recurrent Abortions

Cited by 13 publications

References 25 publications

PPARgamma Expression is Diminished in Macrophages of Recurrent Miscarriage Placentas

PPARgamma Expression is Diminished in Macrophages of Recurrent Miscarriage Placentas

RXRα is upregulated in first trimester endometrial glands of spontaneous abortions unlike LXR and PPARγ

The prostaglandin receptor EP2 determines prognosis in EP3-negative and galectin-3-high cervical cancer cases

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