Effect of Taoren Quyu Decoction on human endometrial cells and its anti-endometriosis activity in rats

Objective: To study the effect of Taoren Quyu Decoction(TQD) on endometrial cells in patients with endometriosis(EMs) and EMs in rats. Methods: A total of 60 female Wistar rats were randomly divided into 4 groups, namely, normal group, model group, positive group and TQD group, each group having 15 rats. Except the normal group, EMs model was established in the other three groups by transplanting the rat autologous endometrium. After 4 weeks of intragastric administration, blood, eutopic and ectopic endometrial tissues of rats in each group were collected to detect the serum levels of estrogen(E2), cancer antigen 125(CA125), endometrial antibody(EMAb), and expressions of microvessel density(MVD), vascular endothelial growth factor(VEGF) and angiopoietin(Ang-2). The volume of endometriosis cyst was determined simultaneously. For the in vitro culture of human endometrial cells, 4 groups, namely, normal group, model group, positive group and TQD group were used. The positive group and TQD group were treated with danazol and TQD respectively. Then 24 h after the treatment, the expressions of survivin and tumor suppressor gene(p53) of each group were detected. Results: The volumes of the endometriosis cysts in the positive group and the TQD group were significantly reduced compared with the model group(P<0.05). The serum levels of E2, CA125 and EMAb, and the expressions of MVD, VEGF and Ang-2 in the model group were significantly increased compared with the normal group(P<0.05); while they were all significantly reduced in the positive group and TQD group(P<0.05). Compared with the normal group, the expression of survivin in the model group was significantly upregulated(P<0.05), and expression of p53 was significantly reduced(P<0.05); compared with the model group, the expressions of survivin in the positive and TQD groups were significantly decreased(P<0.05), and expression of p53 was significantly up-regulated(P<0.05). The difference between positive group and TQD group was not statistically significant(P>0.05). Conclusions: TQD has a significant anti-EMs effect, and its mechanism of action may be related to anti-angiogenesis and promoting apoptosis of ectopic endometrial cell.

Effects of Yimu Shenghuasan Preparation on the Cytochrome P450 in Endometrial Cells and Immune Function of Dairy Cows

In order to investigate the mode of action ofYimu Shenghuasan preparation in endometrial cells of dairy cows, the primary cultured endometrial cells in cows were isolated and the inflammatory models were made by lipopolysaccharide （LPS） induction. The inflammatory cells were treated with gradient concentration of herbal medicine preparation, Yimu Shenghuasan for 48 and 72 h. The expression of cytochrome P450 （CYP450） was detected by Western blot. The amounts of IgG and lgA in sera were also detected in the endometritis of dairy cows. The expression level of CYP450 in the endometrial cells of dairy cow was increased gradually, and the amounts of IgG, IgA were increased significantly as compared with those in the control group. The expression level of CYP450 in the inflammatory cells was increased significantly in the treatment of 2 000 μg mL^-1 of Yimu Shenghuasan after 48 h of treatment.

circRNA3669 promotes goat endometrial epithelial cells proliferation via miR-26a/RCN2 to activate PI3K/AKT-mTOR and MAPK pathways

The development of receptive endometrium(RE) from pre-receptive endometrium(PE) for successful embryo implantation is a complex dynamic process in which the morphology and physiological states of the endometrial epithelium undergo a series of significant changes, including cell proliferation and apoptosis. However, the molecular mechanisms are not yet fully understood. In this study, a higher circRNA3669 level was observed in PE than in RE of goats. Functional assays revealed that this overexpression promoted the proliferation of goat endometrial epithelial cells(GEECs) by activating the expression of genes related to the PI3K/AKT-mTOR and MAPK pathways,thereby inhibiting apoptosis in vitro. Furthermore, circRNA3669 functioned as a competing endogenous RNA(ceRNA) to upregulate Reticulocalbin-2(RCN2) expression at the post-transcriptional level by interacting with and downregulating miR-26a in GEECs. In addition, RCN2, which is highly expressed in the PE of goats, was found to be regulated by β-estradiol(E2) and progesterone(P4). Our results demonstrated that RCN2 also affected the key proteins PI3K, AKT, mTOR, JNK, and P38 in the PI3K/AKT-mTOR and MAPK pathways, thereby facilitating GEECs proliferation and suppressing their apoptosis in vitro. Collectively, we constructed a new circRNA3669-miR-26aRCN2 regulatory network in GEECs, which further provides strong evidence that circRNA could potentially play a crucial regulatory role in the development of RE in goats.

Evaluation of Circulating Endometrial Cells as a Biomarker for Endometriosis

Background： Circulating endometrial cells （CECs） have been reported to be present in the peripheral blood of women with endometriosis （EM）, providing clear and specific evidence of the presence of ectopic lesions. In this study, we established a method with a high detection rate of CECs, assessed the diagnostic value of CECs for EM and compared with serum CA125, and proposed a hypothesis for the pathogenesis of EM from the new perspective of CECs. Methods： The participants were enrolled prospectively from October 2015 to July 2016. The peripheral blood samples were collected from 59 participants, and the blood cells were isolated for immunofluorescence staining via microfluidic chips. The cells that were positive for vimentin/cytokeratin and estrogen/progesterone receptor and negative for CD45 were identified as CECs. The serum CA125 level was tested with electrochemiluminescence immunoassay. Results： The detection rate of CECs reached 89.5% （17/19） in the EM group, which was significantly higher than that of the control group （15.0% [6/40], P 〈 0.001） and was independent of menstrual cycle phases. Furthermore, a positive CEC assay detected 4/5 cases of Stage Ⅰ–Ⅱ EM. In contrast, a positive CA125 test had limited value in detecting EM （13/19, 68.4%） and detected only one case of Stage Ⅰ–Ⅱ EM. Conclusion： CECs are promising biomarkers for EM with great potential for a noninvasive diagnostic assay.

Therapeutic effects of menstrual blood-derived endometrial stem cells on mouse models of streptozotocin-induced type 1 diabetes

BACKGROUND Type 1 diabetes(T1D),a chronic metabolic and autoimmune disease,seriously endangers human health.In recent years,mesenchymal stem cell(MSC)transplantation has become an effective treatment for diabetes.Menstrual bloodderived endometrial stem cells(MenSC),a novel MSC type derived from the decidual endometrium during menstruation,are expected to become promising seeding cells for diabetes treatment because of their noninvasive collection procedure,high proliferation rate and high immunomodulation capacity.AIM To comprehensively compare the effects of MenSC and umbilical cord-derived MSC(UcMSC)transplantation on T1D treatment,to further explore the potential mechanism of MSC-based therapies in T1D,and to provide support for the clinical application of MSC in diabetes treatment.METHODS A conventional streptozotocin-induced T1D mouse model was established,and the effects of MenSC and UcMSC transplantation on their blood glucose and serum insulin levels were detected.The morphological and functional changes in the pancreas,liver,kidney,and spleen were analyzed by routine histological and immunohistochemical examinations.Changes in the serum cytokine levels in the model mice were assessed by protein arrays.The expression of target proteins related to pancreatic regeneration and apoptosis was examined by western blot.RESULTS MenSC and UcMSC transplantation significantly improved the blood glucose and serum insulin levels in T1D model mice.Immunofluorescence analysis revealed that the numbers of insulin+and CD31+cells in the pancreas were significantly increased in MSC-treated mice compared with control mice.Subsequent western blot analysis also showed that vascular endothelial growth factor(VEGF),Bcl2,Bcl-xL and Proliferating cell nuclear antigen in pancreatic tissue was significantly upregulated in MSC-treated mice compared with control mice.Additionally,protein arrays indicated that MenSC and UcMSC transplantation significantly downregulated the serum levels of interferonγand tumor necrosis factorαand upregulated the serum levels of interleukin-6 and VEGF in the model mice.Additionally,histological and immunohistochemical analyses revealed that MSC transplantation systematically improved the morphologies and functions of the liver,kidney,and spleen in T1D model mice.CONCLUSION MenSC transplantation significantly improves the symptoms in T1D model mice and exerts protective effects on their main organs.Moreover,MSC-mediated angiogenesis,antiapoptotic effects and immunomodulation likely contribute to the above improvements.Thus,MenSC are expected to become promising seeding cells for clinical diabetes treatment due to their advantages mentioned above.

Multifactor Regulation on Expressions of MMP-9 and TIMP-1 in Endometrial Stromal Cells

Objective To investigate the regulatory effect of multifactor on the matrix metalloproteinases-9 （MMP-9） and the tissue inhibitor of metalloproteinase-1 （TIMP-1） in endometrial stromal cells. Methods The endometrial stromal cells separated from the proliferative endometrial tissues were incubated with medium alone, 17-β estradiol （E2,10^-8 mol/L）, medroxyprogesterone acetate （MPA, 10^-6 mol/L）, E2（10^-8 mol/L）＋MPA （10^-6 mol/L）, E2 （10^-8 mol/L）＋MPA （10^-6 mol/L）＋RU486 （10^-5 mol/L） or HB-EGF （10 ng/ml） for 48 h respectively. The expressions of MMP-9 and TIMP-1 were detected by in situ hybridization, immunocytochemistry, reverse transcriptase-polymerase chain reaction （RT-PCR） and Western blotting. Results Compared with control group [mRNA, 0. 729 ± 0. 090 （MMP-9） and 1.056± 0.154 （TIMP-1）; protein, 0.545 ±0.086 （MMP-9） and 0.745 ±0.154 （TIMP-1）], expressions of MMP-9 and TIMP-1 in E2 alone, progestin alone or E2 combined with progestin group were respectively：mRNA, 0.413 ± 0.069, 0.402 ± 0.073 and 0.407 ± 0.039; 0.487 ± 0.093, 0.503 ± 0.093 and 0.468 ± 0.075：protein, 0.294 ± 0.076, 0.331 ±0.064 and 0.265 ±0.049; 0.425 ±0.085, 0.397 ±0.065 and 0.435 ± 0.099. RU486 weakened the expression level of down-regulation, while HB-EGF elevated the level of MMP-9 and TIMP-1 after 48 h treatment （mRNA, 0.955 ± 0.068 and 1.396 ± 0.238; protein, 0. 780 ± 0.109 and 0.985 ± 0.165）. Conclusions 1） Both E2 and progestin can down-regulate the expressions of MMP-9 and TIMP-1 in endometrial stromal cells, but RU486 can inhibit the effect. 2） HB-EGF can elevate the level of MMP-9 and TIMP-1. 3） E2, progestin and HB-EGF have effect on the ratio of MM-P/TIMP-1.

Differentially Gene Expression Profile Related to Inflammation in Endometrial Cells Induce by Lipopolysaccharide

Objective To investigate differentially expressed genes related to inflammation in endometrial cells induced by Lipopolysaccharide（LPS）. Methods Normal endometrium in the proliferative phase of specimen from 3 cases for the experiment was collected. The LPS group were treated with 50 μg/ml LPS. Total RNA was extracted using Trizol reagent from cells. RNA quality was assessed by determining the OD260/280 ratio by agarose gel electrophoresis, the chip was scanned by laser scanner. The acquired was analyzed. Results A total of differentially expressed genes were found, these genes were relative to many aspects. Among them, the expression of genes involved in inflammation were up-regulated by LPS, such as overexpression of IL-1β, 8, etc. Conclusion The results indicates that inflammation-related genes may be one of the mechanisms of abnormal uterine bleeding by LPS-induced.

Value of ^(18)F-FDG PET/CT and MRI in diagnosing primary endometrial small cell carcinoma

Primary small cell carcinoma（SCC） is a group of aggressive neoplasms that mainly arise from the lung and digestive tract. Endometrial small cell carcinoma（ESCC） is extremely rare. To our knowledge, less than 90 cases have been reported, and most of these reports were dedicated to describing the clinicopathologic or immunochemical features of ESCC. Herein, we present a new case of ESCC involving a 51-year-old woman and mainly focus on the magnetic resonance imaging（MRI） and positron emission tomography/computed tomography（PET/CT） findings. MRI showed that the uterus was significantly enlarged（11.6 cm × 11.1 cm × 14.4 cm）, and a giant irregular mass（7.5 cm × 8.4 cm × 8.5 cm） was observed in the uterine cavity. The lesion demonstrated an extremely low apparent diffusion coefficient（ADC） value [（0.553±0.088）×10^–3 mm^2/s] and a high FDG uptake value（22.7）. Multiple metastatic lymph nodes（LNs） were identified at different positions, with diameters ranging from 0.3 to 2.8 cm and a maximum standardized uptake value（SUV max） ranging from 6.9 to 19.3.

Endometrial squamous cell carcinoma originating from the cervix: A case report

BACKGROUND Cervical squamous cell carcinoma(SCC)is the most common type of cervical carcinoma and is generally derived from a precancerous stage called cervical high-grade squamous intraepithelial lesion(HSIL).Usually,the cancer metastasizes through lymphatic or hematogenous dissemination,but rarely spreads upward into the uterus.Here,we report a case of cervical HSIL extending into the endometrium and finally progressing to SCC in the uterine cavity.CASE SUMMARY A 57-year-old postmenopausal woman visited our department and requested a routine cervical check-up.Four years ago,she had undergone a cervical loop electrosurgical excision procedure because of HSIL found during the gynecological examination,and she had not been checked again since.This time,a relapse of the cervical HSIL was diagnosed along with uterine pyometra and endometrial polyps.After 2 wk of antibiotic treatment,a laparoscopic hysterectomy was performed,and the final pathological examination revealed that the cervical HSIL had spread directly upward into the uterine cavity,gradually developing into cervical SCC in the endometrium.CONCLUSION Cervical HSIL/SCC can directly spread upward into the uterus with the most common symptoms of pyometra and cervical stenosis.More attention should be given to the early detection and prevention of this disease.

The influence of insulin on secretion of IGF-Ⅰand IGFBP-Ⅰin cultures of human endometrial stromal cells

s To study the influence of insulin on IGF Ⅰ and IGFBP Ⅰ secretion of the hum an endometrial stromal cells Methods Late proliferative phase endometrial stromal cells were isolated from endometriu m tissues and then cultured for 24 h in Hams F 12 only as a control and in Hams F 12 with different concentrations of estradiol (E2) and insulin (INS) as trea ted groups Simultaneously, the endometrial stromal cells from late secretory phase endometrium were cultured for 24 h in Hams F 12 only as a control and in Hams F 12 supplemented with different concentrations of progesterone (P) and i nsulin as treated groups After 24 h of culturing, the mediums were collected f or either IGF Ⅰ or IGFBP Ⅰ assays Result The concentrations of IGF Ⅰ in medium from cultured endometrial stromal cells i n the proliferative phase were 0 78±0 47 ng/ml in the hormone free control g roup; 1 44±0 59 ng/ml and 1 39± 0 33 ng/ml in 100 pg/ml E2 group and 20 μU /ml INS group, which was higher than that of the control group ( P <0 05 and P <0 01, respectively) The IGF Ⅰ concentration in the 100 μU/ml INS group was 2 03±0 53 ng/ml, which was higher than that of the 20 μU/ml INS group ( P <0 01) Levels of IGF Ⅰ in the 100 pg/ml E2 plus 20 μU/ml INS gro up was 2 18±0 36 ng/ml, which was significantly higher than that of the 20 μU/ml INS and 100 pg/ml E2 group ( P <0 01), but lower than that of the 100 pg/ml E2 p lus 100 μU/ml INS group (3 42±0 75 ng/ml), P <0 01 The concentration o f IGFBP Ⅰ in medium from cultured endometrial stromal cells in the secretory ph a se was 2 50±1 39 ng/ml in the hormone free control group and 5 44±2 09 ng /ml in the 10 pg/ml P group, which was significantly higher than that of the con trol ( P <0 01) IGFBP Ⅰ concentration in 20 μU/ml INS group was 0 1 6±0 58 ng/ml, which was lower compared with control, but higher compared with the 100 μU/ml INS group ( P <0 01) The level of IGFBP Ⅰ in the 10 ng/ml P plu s 20 μU/ml INS group was 2 10±1 17 ng/ml, lower compared with the 10 ng/ml P gr oup, but higher compared with the 10 pg/ml P plus 100 μU/ml INS group, P <0 01 Conclusions Insulin can stimulate basal (without hormone) and E2 stimulated IGF Ⅰ secreti on in cultured stromal cells from human late proliferative endometrium in a dose dependent manner Insulin can suppress basal (without hormone) and P stimula ted IGFBP Ⅰ secretions in cultured stromal cells from human secretory endomet rium in a dose dependent manner

Adenomyosis-derived extracellular vesicles endow endometrial epithelial cells with an invasive phenotype through epithelial-mesenchymal transition

Extracellular vesicles from highly metastatic tumor cells have been shown to mediate epithelial-mesenchymal transition(EMT)-related events in recipient cells.In endometrial epithelial cells,EMT processes are known to be involved in the development of adenomyosis.We aimed to investigate whether adenomyosis-derived extracellular vesicles(AMEVs)are able to induce an EMT process in endometrial epithelial cells.In this study,AMEVs were isolated from patients with adenomyosis and characterized by transmission electron microscopy,Western blot,and nanoparticle tracking.Primary endometrial epithelial cells(EECs)were derived from normal endometrium tissues from patients with leiomyoma and co-cultured with AMEVs in vitro.AMEV uptake was examined by fluorescence confocal microscopy.The invasion of EECs was confirmed by Transwell assay.Immunohistochemistry,Western blot,and qRT-PCR were performed on EECs to illustrate the expression levels of cytokeratin 19,E-cadherin,vimentin,and zinc finger E-boxbinding homeobox 1(ZEB1).The results indicated that the cellular fluorescence intensity gradually increased after 48 h of co-culture,but decreased after 72 h.After co-culturing with AMEVs for 72 h,EECs expressed significantly lower levels of cytokeratin 19 and E-cadherin,and significantly higher levels of vimentin and ZEB1.Together these results demonstrated that AMEVs induce an EMT process and enhance the invasion of EECs.These changes may contribute to the pathogenesis and progression of adenomyosis.

Human adult stem cells from menstrual blood and endometrial tissue

The article "Plasticity of human menstrual blood stem cells derived from the endometrium" by Lin et al. (2011), published in Journal of Zhejiang University- SCIENCE B (Biomedicine & Biotechnology),

Differentiation of Human Adipose-Derived Stem Cells into Endometrial Epithelial Cells

Objective:This study aimed to investigate the differentiation of human adipose-derived stem cells(hASCs)into endometrial epithelial cells(EECs)under certain induction conditions and to a further step provide a promising approach for ASCs in clinical practice to the treatment of severe intrauterine adhesion.Methods:Four groups of hASCs were separately cultured as follows:in Group 1,hASCs were cultured in a control medium(5%fetal bovine serum[FBS]+α-minimum Eagle’s medium[α-MEM]);in Group 2,hASCs were cultured in an induction medium(5%FBS+α-MEM+[1×10-7 mol/L 17β-estradiol]+10 ng/mL transforming growth factorβ1[TGF-β1]+10 ng/mL epidermal growth factor[EGF]+10 ng/mL platelet-derived growth factor BB[PDGF-BB]);in Group 3,hASCs and human endometrium cells(hEMCs)were cocultured in the control medium;and in Group 4,hASCs and hEMCs were cocultured in the induction medium.Results:When cocultured with hEMCs,the morphology of hASCs became similar with EECs,and the addition of factors such as EGF,TGFβ,PDGF-BB,and 17β-estradiol promoted differentiation.This study,for the first time,demonstrated estrogen receptor(ER)αand ERβexpression in hASCs and preliminarily explored changes in ERα,ERβ,β-catenin,and H19 mRNA expression during hASC differentiation.Furthermore,we concluded that H19 mRNA expression was negatively correlated with differentiation,which is seemingly related to the estrogen signaling pathway.Conclusions:hASCs revealed the potential for differentiating to EECs when cocultured with hEMCs.

Roles of Regulatory T Cells in Pathogenesis of Endometriosis

Numerous studies have shown aberrant immune cell function in endometriosis,including T cells,B cells,natural killer cells,and macrophages(MΦ).These alterations are thought to be induced by various mechanisms that promote the disease.Regulatory T cells(Tregs)may account for a decreased ability of newly recruited leukocytes to initiate effective immune responses against viable endometrial fragments,permitting their survival.Tregs differentiate during the development of endometriosis,which confer immunosuppression or play other roles in disease progression.In this review,we provide an overview of the regulation and roles of Tregs in endometriosis.These data provide further scientific evidence for the altered immune response in endometriosis,which could be a potential target in the treatment of endometriosis.This review could create new diagnostic strategies and effective immune-targeted therapies for this highly prevalent disease.Recent progress in the field indicates that these goals may be achieved in the future.

Value of T cell receptor gamma alternate reading frame protein and keratin 5 in endometrial carcinoma

Background Tumors with different gene expression develop and progress in different ways. To deepen our understanding of the progression in endometrial cancer, and provide a useful tool for accurate diagnosis and prognosis assessment, we identified the new molecular prognostic markers in endometrial carcinoma and analyzed the relationship of them with clinical and pathological features of endometrial carcinoma. Methods Ninety-four cases of endometrial endometrioid adenocarcinoma with complete data from the Peking University People＇s Hospital from 2000 to 2008 and 40 cases of normal endometrium were enrolled. Among these, 30 endometrial endometrioid adenocarcinoma samples of different International Federation of Gynecology and Obstetrics （FIGO） stage were selected for further Agilent genome-wide microarray analysis. Significance analysis of microarrays （SAM） was used to identify genes that are significantly associated with tumor progress. Immunohistochemistry was utilized to identify the genes of interest in endometrial carcinoma and normal endometrium. The relationship between the genes and the age, clinical stage, histological grade, myometrium invaded depth, lymph node metastasis status, and the expression of ER, PR, P53, and PTEN were analyzed by X2 test. Results Analysis between FIGO 1988 stage I and stage III identified a 362-gene ＂progress signature＂; 171 downregulated and 191 up-regulated genes. Among the alterative genes, TARP （T cell receptor gamma alternate reading frame protein） and KRT5 （keratin 5） decreased 3.57 fold and 5.8 fold in FIGO stage III patients. The expression of TARP in endometrial carcinoma increased compared to normal endometrium, while that of KRT5 decreased （P〈0.05）. The expression of TARP and KRT5 decreased when stage, histological grading, myometrium invaded depth increased （P〈0.05）. In the cases with lymph node metastasis, the expression of TARP decreased, while the expression of KRT5 did not differ （both P〈0.05） both. The expression of P53 had a negative relationship with the expression of KRT5 （P〈0.05）, but not with the expression of TARP （P〉0.05）. There was no correlation between the expression of TARP and KRT5 and the expression of ER, PR, PTEN （all P〉0.05）. There was no significant difference in TARP and KRT5 expression in patients aged 50 or younger and patients older than 50 （P〉0.05）. Conclusion The expression of TARP and KRT5 was correlated with the progress of endometrial cancer and their role needs further study.

Expression of Cytokeratin,Actin and Endocrine Hormones in Human Hatched Blastocyst Implantation Model in vitro

Objective To investigate the expression of cytokeratin,actin and hCG,E2 and P of human hacthed blastocysts in the model.Methods Human hatched blastocysts were co-cultured with human endometrial decidualization stromal cell monolayer.The process of orientation,attachment,outgrowth and invasion in morphology were observed.Immunofluorescence staining for cytokeratin and actin,immunofluorescence measurement of hCG and radioimmunoassay measurement of E2 and P were performed.Results Blastocysts attached to stromal cell layer after 5h in co-culture.After 24h in co-culture,the trophoblast protruded from two opposite poles of the blastocyst and underwent outgrowth into the stromal cell monolayer,blastocyst became bigger and invaded finally into the stromal cells.After 48h in co-culture,cytokeratin staining was only visible in trophoblast but not stromal cells,actin staining was visible in both of trophoblast and stromal cells with distinct conformation and structure.Stromal cells had prominent linear actin filaments,aligned along the long axis of the cells.Cytokeratin staining in trophoblast cells was localized in short filaments arranged in a mesh.hCG,E2 and P levels in the supernate of stromal cell-blastocyst co-culture were higher than the supernate from blastocyst cultured only （P〈0.01）.Conclusion An implantation model for the reflection of the process of human blastocysts attachment,outgrowth and invasion into stromal cells has been established in vitro.Cytokeratin,actin and hCG,E2 and P take place corresponding changes in the human implantation blastocyst cells.

Indoleamine 2,3-Dioxygenase in Endometriosis

Endometriosis(EMS)is a chronic inflammatory and estrogen-dependent gynecological disease characterized by the presence of endometrial tissue outside the uterine cavity.Although it is a benign disease,EMS is tumor-like in several aspects,which include unrestrained growth,decreased apoptosis,and aggressive invasion.EMS involves endocrine disorders and immunological factors.Indoleamine 2,3-dioxygenase(IDO)is an intracellular enzyme that catalyzes the initial and rate-limiting step of the metabolism of tryptophan.IDO is a potential candidate facilitating EMS development.Increased IDO expression in both eutopic and ectopic endometria of women with EMS is biologically important in aspects,which include regulation of endometrial stromal cell function and modulation of adjacent local immunocytes to generate a supportive microenvironment.In turn,the expression of IDO can be regulated by the complex endocrine-immune microenvironment networks in endometrial lesions.Here,we systematically review the roles of IDO in EMS to explore its pathological implications and treatment potential.

Unique and independent role of the GABAB1 subunit in embryo implantation and uterine decidualization in mice

Embryo implantation and decidualization are crucial for successful pregnancy,which include multiple genes and signaling pathways,while the precise mechanism regarding embryo implantation and decidualization has yet to be explored.The GABA which activates GABA_(A)or GABA_(B)receptors has been found playing an important role in early pregnancy.Here we seek to investigate whether GABA_(B)receptors participate in embryo implantation in mice.This study first characterized the spatiotemporal expression pattern of GABA_(B)receptors in the uterus during the peri-implantation period and found that GABA_(B1)expression was drastically upregulated in stromal cells on days 4e6,a period of embryo implantation and early stages of decidualization.Embryo delayed implantation and oil-induced decidualization models were further used to confirm that the GABA_(B1)was associated with embryo implantation and decidualization.We also found estrogen or progesterone had no directly effect on expression of GABA_(B1)in ovariectomized model.Because we were unable to detect significant GABA_(B2)which couples with GABA_(B1)to form whole GABA_(B)receptors,and the agonist and antagonist of whole GABA_(B)receptors had weak effect on the proliferation and differentiation of stromal cells as well,we excluded the possibility whole GABA_(B)receptors function,and concluded it should be non-classical signals of GABA_(B1)involving in embryo implantation and decidualization.Future studies should focus on investigating the roles and mechanisms of GABA_(B1)during embryo implantation and decidualization.

Decidualization and Related Pregnancy Complications

Decidualization is the differentiation of endometrial stromal cells into secretory decidual stromal cells.Human decidualization involves some amount of signaling molecules and pathways as well as genetic reprogramming,which is driven by the postovulatory rise in progesterone levels and local cyclic adenosine monophosphate production.Decidualization extends from the primary decidual zone to the secondary decidual zone,and then exits through apoptosis.Evidences support that decidual fibroblasts function as the pool of decidual stromal cells during pregnancy.Decidualization undergoes an acute inflammatory phase,an anti-inflammatory secretory phase to the final recession phase.The decidualization of the inner layer of endometrium,termed decidua,is the most critical determinant of pregnancy success,which can promote placenta formation,modulate immune tolerance,foster resistance to oxidative stress,sense embryo quality,and control labor.Failure to adequate decidualization in terms of hormones,biochemistry,and immunology leads to adverse pregnancy outcomes,including diseases such as preeclampsia,miscarriage,premature labor,repeated implantation failures,and some age-related decline in reproductive capacity.The development of animal models and in vitro culture systems combined with emerging technologies provides a powerful system to explore the mechanism of decidualization.However,decidualization is a dynamic,multi-step process,and translating of current research progress into disease predictions and interventions for pregnancy complications remains to be achieved.The study of periodic regeneration and spontaneous decidualization of the endometrium will be beneficial to the diagnosis and treatment of pregnancy diseases.