scholarly journals Role of Versican in the Pathogenesis of Peritoneal Endometriosis

2016 ◽  
Vol 101 (11) ◽  
pp. 4349-4356 ◽  
Author(s):  
Hirohiko Tani ◽  
Yukiyasu Sato ◽  
Masashi Ueda ◽  
Yumiko Miyazaki ◽  
Koh Suginami ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Chinese Hamster Ovary Cells ◽  
Cell Monolayer ◽  
Chinese Hamster ◽  
Endometrial Stromal Cells ◽  
Matrigel Invasion ◽  
Molecular Alterations ◽  
Peritoneal Endometriosis

Context: Sampson’s theory cannot explain why only some cycling women develop peritoneal endometriosis. Few studies have focused on the pelvic peritoneum, which receives regurgitated endometrial tissues. We hypothesized that molecular alterations in the peritoneum are involved in the development of peritoneal endometriosis and conducted a microarray analysis to compare macroscopically normal peritoneum sampled from women with peritoneal endometriosis (endometriotic peritoneum) and those without (non-endometriotic peritoneum). Versican, a major proteoglycan component of the extracellular matrix, is one of the molecules up-regulated in endometriotic peritoneum. Objective: To investigate the role of versican in peritoneal endometriosis. Design, Patients, and Main Outcome Measure: Endometriotic peritoneum and non-endometriotic peritoneum were subjected to RT-PCR, immunostaining, and Western blotting. The versican V1 isoform was stably transfected into Chinese hamster ovary cells (CHO-V1), and the effects of CHO-V1-derived conditioned medium (V1-CM) on primary human endometrial stromal cells were investigated with attachment, invasion, and proliferation assays. The effects of peritoneal fluid collected from endometriotic women (endometriotic PF) or cytokines/growth factors, which were shown to be elevated in endometriotic PF, on versican expression in a human peritoneal cell line (HMrSV5) were also examined. Results: Versican V1 expression levels were significantly higher in endometriotic peritoneum. In vitro, V1-CM promoted attachment to the HMrSV5 cell monolayer as well as the Matrigel invasion of endometrial stromal cells. Although versican V1 expression was up-regulated by TGF-β1 in HMrSV5 cells, it remained unchanged in endometriotic PF. Conclusions: Our results suggest the involvement of peritoneal versican in the development of peritoneal endometriosis.

scholarly journals The Role of the FOXO1/β2-AR/p-NF-κB p65 Pathway in the Development of Endometrial Stromal Cells in Pregnant Mice under Restraint Stress

2021 ◽  
Vol 22 (3) ◽  
pp. 1478
Author(s):  
Jiayin Lu ◽  
Yaoxing Chen ◽  
Zixu Wang ◽  
Jing Cao ◽  
Yulan Dong
Keyword(s):  
Oxidative Stress ◽  
Stromal Cells ◽  
Restraint Stress ◽  
Target Genes ◽  
Mrna Levels ◽  
Endometrial Stromal Cells ◽  
Protein Levels ◽  
Pregnant Mice

Restraint stress causes various maternal diseases during pregnancy. β2-Adrenergic receptor (β2-AR) and Forkhead transcription factor class O 1 (FOXO1) are critical factors not only in stress, but also in reproduction. However, the role of FOXO1 in restraint stress, causing changes in the β2-AR pathway in pregnant mice, has been unclear. The aim of this research was to investigate the β2-AR pathway of restraint stress and its impact on the oxidative stress of the maternal uterus. In the study, maternal mice were treated with restraint stress by being restrained in a transparent and ventilated device before sacrifice on Pregnancy Day 5 (P5), Pregnancy Day 10 (P10), Pregnancy Day 15 (P15), and Pregnancy Day 20 (P20) as well as on Non-Pregnancy Day 5 (NP5). Restraint stress augmented blood corticosterone (CORT), norepinephrine (NE), and blood glucose levels, while oestradiol (E2) levels decreased. Moreover, restraint stress increased the mRNA levels of the FOXO family, β2-AR, and even the protein levels of FOXO1 and β2-AR in the uterus and ovaries. Furthermore, restraint stress increased uterine oxidative stress level. In vitro, the protein levels of FOXO1 were also obviously increased when β2-AR was activated in endometrial stromal cells (ESCs). In addition, phosphorylated-nuclear factor kappa-B p65 (p-NF-κB p65) and its target genes decreased significantly when FOXO1 was inhibited. Overall, it can be said that the β2-AR/FOXO1/p-NF-κB p65 pathway was activated when pregnant mice were under restraint stress. This study provides a scientific basis for the origin of psychological stress in pregnant women.

scholarly journals Downregulation of decidual SP1 and P300 is associated with severe preeclampsia

2018 ◽  
Vol 60 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Yachao Zhang ◽  
Jieqiong Yang ◽  
Shijian Lv ◽  
Dong-Qin Zhao ◽  
Zi-Jiang Chen ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Rna Interference ◽  
Growth Factor ◽  
Tissue Factor ◽  
Stromal Cells ◽  
Vascular Endothelial ◽  
Endometrial Stromal Cells ◽  
Endothelial Growth Factor

Preeclampsia (PE) is a pregnancy-induced disorder characterized by hypertension and proteinuria after 20 weeks of gestation, affecting 5–7% of pregnancies worldwide. So far, the etiology of PE remains poorly understood. Abnormal decidualization is thought to contribute to the development of PE. SP1 belongs to the Sp/KLF superfamily and can recruit P300 to regulate the transcription of several genes. SP1 is also very important for decidualization as it enhances the expression of tissue factor. In this study, we investigated the expression of SP1 and P300 in deciduae and their relationship with PE. A total of 42 decidua samples were collected, of which 21 were from normal pregnant (NP) and 21 from severe PE. SP1 and P300 expression in deciduae and the levels of SP1 and P300 in cultured human endometrial stromal cells (hESCs) and primary hESCs during decidualization were determined. To further investigate the role of SP1 and P300 in human decidualization, RNA interference was used to silence SP1 and P300 in hESCs and primary hESCs. The following results were obtained. We found that the expressions of SP1 and P300 were reduced in decidual tissues with PE compared to those from NP. In thein vitromodel of induction of decidualization, we found an increase in bothSP1andP300levels. Silencing ofSP1andP300resulted in abnormal decidualization and a significant reduction of decidualization markers such as insulin-like growth factor-binding protein1 and prolactin. Furthermore, the expression of vascular endothelial growth factor was also decreased uponSP1andP300silencing. Similar results were observed in primary hESCs. Our results suggest that SP1 and P300 play an important role during decidualization. Dysfunction of SP1 and P300 leads to impaired decidualization and might contribute to PE.

scholarly journals IL15 promotes growth and invasion of endometrial stromal cells and inhibits killing activity of NK cells in endometriosis

Reproduction ◽  
2016 ◽  
Vol 152 (2) ◽  
pp. 151-160 ◽  
Author(s):  
Jia-Jun Yu ◽  
Hui-Ting Sun ◽  
Zhong-Fang Zhang ◽  
Ru-Xia Shi ◽  
Li-Bing Liu ◽  
...  
Keyword(s):  
Nk Cells ◽  
Stromal Cells ◽  
Culture System ◽  
Immune Escape ◽  
Cell Counting ◽  
Endometrial Stromal Cells ◽  
Endometrial Cells ◽  
Matrigel Invasion ◽  
Abnormal Immune Response

Endometriosis (EMS) is associated with an abnormal immune response to endometrial cells, which can facilitate the implantation and proliferation of ectopic endometrial tissues. It has been reported that human endometrial stromal cells (ESCs) express interleukin (IL)15. The aim of our study was to elucidate whether or not IL15 regulates the cross talk between ESCs and natural killer (NK) cells in the endometriotic milieu and, if so, how this regulation occurs. The ESC behaviors in vitro were verified by Cell Counting Kit-8 (CCK-8), Annexin/PI, and Matrigel invasion assays, respectively. To imitate the local immune microenvironment, the co-culture system between ESCs and NK cells was constructed. The effect of IL15 on NK cells in the co-culture unit was investigated by flow cytometry (FCM). In this study, we found that ectopic endometrium from patients with EMS highly expressed IL15. Rapamycin, an autophagy inducer, decreased the level of IL15 receptors (i.e. IL15Rα and IL2Rβ). IL15 inhibits apoptosis and promotes the invasiveness, viability, and proliferation of ESCs. Meanwhile, a co-culture with ESCs led to a decrease in CD16 on NK cells. In the co-culture system, IL15 treatment downregulated the levels of Granzyme B and IFN-γ in CD16+NK cells, NKG2D in CD56dimCD16-NK cells, and NKP44 in CD56brightCD16-NK cells. On the one hand, these results indicated that IL15 derived from ESCs directly stimulates the growth and invasion of ESCs. On the other hand, IL15 may help the immune escape of ESCs by suppressing the cytotoxic activity of NK cells in the ectopic milieu, thereby facilitating the progression of EMS.

scholarly journals Inhibition of TPPP3 attenuates β-catenin/NF-κB/COX-2 signaling in endometrial stromal cells and impairs decidualization

2019 ◽  
Vol 240 (3) ◽  
pp. 417-429 ◽  
Author(s):  
Vinay Shukla ◽  
Jyoti Bala Kaushal ◽  
Pushplata Sankhwar ◽  
Murli Manohar ◽  
Anila Dwivedi
Keyword(s):  
Stromal Cells ◽  
Embryo Implantation ◽  
Nuclear Accumulation ◽  
Decidual Cell ◽  
Endometrial Stromal Cells ◽  
Cox 2 ◽  
Sirna Knockdown

Embryo implantation and decidualization are critical events that occur during early pregnancy. Decidualization is synchronized by the crosstalk of progesterone and the cAMP signaling pathway. Previously, we confirmed the role of TPPP3 during embryo implantation in mice, but the underlying role and mechanism of TPPP3 in decidualization has not yet been understood. The current study was aimed to investigate the role of TPPP3 in decidualization in vivo and in vitro. For in vivo experiments, decidual reaction was artificially induced in the uteri of BALB/c mice. TPPP3 was found to be highly expressed during decidualization, whereas in the uteri receiving TPPP3 siRNA, decidualization was suppressed and the expression of β-catenin and decidual marker prolactin was reduced. In human endometrium, TPPP3 protein was found to be predominantly expressed in the mid-secretory phase (LH+7). In the primary culture of human endometrial stromal cells (hESCs), TPPP3 siRNA knockdown inhibited stromal-to-decidual cell transition and decreased the expression of the decidualization markers prolactin and IGFBP-1. Immunofluorescence and immunoblotting experiments revealed that TPPP3 siRNA knockdown suppressed the expression of β-catenin, NF-κB and COX-2 in hESCs during decidualization. TPPP3 inhibition also decreased NF-kB nuclear accumulation in hESCs and suppressed NF-κB transcriptional promoter activity. COX-2 expression was significantly decreased in the presence of a selective NF-kB inhibitor (QNZ) implicating that NF-kB is involved in COX-2 expression in hESCs undergoing decidualization. TUNEL assay and FACS analysis revealed that TPPP3 knockdown induced apoptosis and caused loss of mitochondrial membrane potential in hESCs. The study suggested that TPPP3 plays a significant role in decidualization and its inhibition leads to the suppression of β-catenin/NF-κB/COX-2 signaling along with the induction of mitochondria-dependent apoptosis.

scholarly journals CXCL16/CXCR6 interaction promotes endometrial decidualization via the PI3K/AKT pathway

Reproduction ◽  
2019 ◽  
Vol 157 (3) ◽  
pp. 273-282 ◽  
Author(s):  
Jie Mei ◽  
Yuan Yan ◽  
Shi-Yuan Li ◽  
Wen-Jie Zhou ◽  
Qun Zhang ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Stromal Cells ◽  
Akt Pathway ◽  
New Paradigm ◽  
Akt Inhibitor ◽  
Endometrial Stromal Cells ◽  
Underlying Mechanisms ◽  
Molecular Crosstalk

Decidualization renders the endometrium transiently receptive to an implanting blastocyst although the underlying mechanisms remain incompletely understood. The aim of this study was to determine the role of chemokine CXCL16 and its receptor CXCR6 in the decidualization during pregnancy. Here, the expression of CXCL16 was investigated in endometrial tissues, decidua and placenta in this study. Compared with endometrial tissue, protein expression of CXCL16 was significantly higher in tissues from the fertile control samples, especially in villus. Meanwhile, the primary trophoblast cells and decidual stromal cells (DSCs) secreted more CXCL16 and expressed higher CXCR6 compared to endometrial stromal cells (ESCs) in vitro. Stimulation with the inducer of decidualization (8-bromoadenosine 3′,5′-cyclic with medroxyprogesterone acetate, 8-Br-cAMP plus MPA) significantly upregulated the expression of CXCL16 and CXCR6 in ESCs in vitro. After treatment with exogenous recombinant human CXCL16 (rhCXCL16) or trophoblast-secreted CXLC16, decidualised ESCs showed a significant decidual response, mainly characterised by increased prolactin (PRL) secretion. Simultaneously, PI3K/PDK1/AKT/Cyclin D1 pathway in decidualised ESCs were activated by rhCXCL16, and AKT inhibitor GS 690693 abolished the PRL secretion of ESCs that was triggered by rhCXCL16. Finally, the impaired CXCL16/CXCR6 expression could be observed at the maternal–foetal interface from patients who have experienced spontaneous abortion. This study suggests that the CXCL16/CXCR6 axis contributes to the progression of ESC decidualization by activating PI3K/PDK1/AKT/Cyclin D1 pathway. It unveils a new paradigm at the maternal–foetal interface in which CXCL16 is an initiator for the molecular crosstalk that enhances decidualization of ESCs.

scholarly journals Decidualization is Impaired in Endometrial Stromal Cells from Uterine Rudiments in Mayer-Rokitansky-Küster-Hauser Syndrome

2017 ◽  
Vol 41 (3) ◽  
pp. 1083-1097 ◽  
Author(s):  
Sara Y. Brucker ◽  
Simone Eisenbeis ◽  
Juliana König ◽  
Melanie Lamy ◽  
Madhuri S. Salker ◽  
...  
Keyword(s):  
Stromal Cells ◽  
University Hospital ◽  
Marker Genes ◽  
Proliferative Capacity ◽  
Receptor Function ◽  
Hormonal Stimulation ◽  
Endometrial Stromal Cells ◽  
Potential Sign

Background/Aims: Uterine rudiments from patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) contain all tissues typically found in the uterus. Endometrium from the rudiments predominantly exhibits basalis-like features, and endometrial proliferative capacity in patients’ epithelium and stroma is significantly lower. Methods: This single-center, prospective study conducted at a major German university hospital compared in-vitro decidualization in cultured ESCs from MRKHS patients and hysterectomy controls. Primary ESC cultures were established from both sources. Hormone-induced prolactin and IGFBP-1 secretion served as a measure of their ability to undergo decidualization in response to hormonal stimulation. Expression levels of 8 key marker genes of decidualization were also determined. Results: At day 9, mean secretion of prolactin and IGFBP-1 was significantly reduced by 89.0% and 99.5%, respectively, in MRKHS ESCs vs. hysterectomy controls, both indicating impaired decidualization of MRKHS ESCs. Key decidual markers confirmed impaired decidualization in MRKHS patients. Conclusion: Our results indicate that the ESCs from MRKHS patients lack hormone responsiveness as a potential sign of dysfunctional hormone receptor function, which may also play a role in the onset of MRKHS. Further studies are needed to corroborate our findings, directly address receptor function, and elucidate the role of other potential determinants of uterine development and adult function.

scholarly journals Long Noncoding RNA UCA1 Is Related to Autophagy and Apoptosis in Endometrial Stromal Cells

2021 ◽  
Vol 10 ◽  
Author(s):  
Lili Jiang ◽  
Yahui Wan ◽  
Ziyi Feng ◽  
Da Liu ◽  
Ling Ouyang ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Research Question ◽  
Pcr Analysis ◽  
Endometrial Stromal Cells ◽  
Qrt Pcr ◽  
Cancer Tissues

Research QuestionThe expression of the long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) in embryonic tissues is higher than that in most cancer tissues, such as bladder cancer, indicating that RNA is a carcinoembryonic antigen. However, there are no published reports on the role of UCA1 in endometriosis (EMS). Therefore, to address this gap in knowledge, we assessed the potential role of lncRNA UCA1 in the pathogenesis and progression of EMS.DesignTo verify the expression of UCA1 in EMS, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used. RNA interference (siRNA) was used to study the biological function of UCA1 in EMS in vitro.ResultsqRT-PCR analysis showed that the expression of lncRNA UCA1 in EMS was increased (P<0.01). Knockdown of UCA1 in vitro significantly inhibited the proliferation of endometrial stromal cells (ESCs) and induced autophagy and apoptosis.ConclusionUCA1 is highly expressed in EMS and promotes the proliferation of ESCs but suppresses autophagy and apoptosis. In EMS, UCA1 may be a prognostic marker and therapeutic target.

scholarly journals Regulation and Function of Laminin A5 during Mouse and Human Decidualization

2021 ◽  
Vol 23 (1) ◽  
pp. 199
Author(s):  
Zhen-Shan Yang ◽  
Hai-Yang Pan ◽  
Wen-Wen Shi ◽  
Si-Ting Chen ◽  
Ying Wang ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Stromal Cells ◽  
Basement Membranes ◽  
Pivotal Role ◽  
Cellular Phenotype ◽  
Mouse Uterus ◽  
Endometrial Stromal Cells ◽  
And Function

Decidualization is essential to the establishment of pregnancy in rodents and primates. Laminin A5 (encoding by Laminin α5) is a member of the laminin family, which is mainly expressed in the basement membranes. Although laminins regulate cellular phenotype maintenance, adhesion, migration, growth, and differentiation, the expression, function, and regulation of laminin A5 during early pregnancy are still unknown. Therefore, we investigated the expression and role of laminin A5 during mouse and human decidualization. Laminin A5 is highly expressed in mouse decidua and artificially induced deciduoma. Laminin A5 is significantly increased under in vitro decidualization. Laminin A5 knockdown significantly inhibits the expression of Prl8a2, a marker for mouse decidualization. Progesterone stimulates the expression of laminin A5 in ovariectomized mouse uterus and cultured mouse stromal cells. We also show that progesterone regulates laminin A5 through the PKA-CREB-C/EBPβ pathway. Laminin A5 is also highly expressed in human pregnant decidua and cultured human endometrial stromal cells during in vitro decidualization. Laminin A5 knockdown by siRNA inhibits human in vitro decidualization. Collectively, our study reveals that laminin A5 may play a pivotal role during mouse and human decidualization via the PKA-CREB-C/EBPβ pathway.

scholarly journals Testosterone inhibits matrix metalloproteinase-1 production in human endometrial stromal cells in vitro

Reproduction ◽  
2007 ◽  
Vol 133 (6) ◽  
pp. 1233-1239 ◽  
Author(s):  
Tomonori Ishikawa ◽  
Tatsuya Harada ◽  
Toshiro Kubota ◽  
Takeshi Aso
Keyword(s):  
Matrix Metalloproteinase ◽  
Stromal Cells ◽  
Human Endometrium ◽  
Dependent Manner ◽  
Endometrial Stromal Cells ◽  
Functional Changes ◽  
Matrix Metalloproteinase 1 ◽  
Human Uterine Endometrium

Androgen receptor (AR) is reported to be expressed in human uterine endometrium, but not much information is available on the role of androgens in human endometrium. The purpose of this study is to investigate the role of androgens in the regulation of matrix metalloproteinase (MMP)-1, which is one of the important MMPs for menstruation and embryo implantation in human endometrium. Human endometrial stromal cells (HESCs) were obtained from human endometrium by enzymatic dissociation method. Purified HESCs were incubated with 17β-estradiol (E2), testosterone, or E2 + testosterone. Progestins (natural progesterone or medroxyprogesterone acetate) or vehicle (dimethyl sulfoxide) were also added to the media instead of testosterone. Furthermore, hydroxyflutamide (FLU),a specific AR antagonist, was also supplemented to cultured media. The amounts of MMP-1 in cultured media and in HESC lysates were examined by ELISA measurements and western blotting analysis respectively. The expression of ARmRNA in HESCs RNA was analyzed by RT-PCR. Testosterone significantly inhibited MMP-1 in both cultured media and cell lysates in a dose-dependent manner. Progestins also inhibited MMP-1. Furthermore, FLU completely recovered the decrease of MMP-1 induced by testosterone. ARmRNA was detected in all HESCs RNA. The present study demonstrated that the secretion and production of MMP-1 in HESCsin vitrowere inhibited by testosterone through androgen receptors in a manner similar to that seen for progesterone. These findings indicate that androgen may play an important role in morphological and functional changes of human endometrium.

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