Expression of the gamma 2 chain of laminin-332 in eutopic and ectopic endometrium of patients with endometriosis.
; Nisolle, Michelle ; et al
in Reproductive biology and endocrinology (2013), 11(1), 94
BACKGROUND: Endometrial cells, which are shed by retrograde menstruation, may aberrantly express molecules involved in invasion and migration, leading to endometriosis. The aim of this study was to ... [more ▼]
BACKGROUND: Endometrial cells, which are shed by retrograde menstruation, may aberrantly express molecules involved in invasion and migration, leading to endometriosis. The aim of this study was to investigate the expression of the laminin gamma 2 chain (LAMC2) in the tissues of women with and without endometriosis. METHODS: Endometrial biopsy specimens were collected from healthy volunteers and from endometriosis patients. Biopsy specimens from the corresponding endometriotic lesions were also collected. The expression of laminin gamma 2 chain was evaluated by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Endometrial tissue from women with or without endometriosis showed constitutive expression of LAMC2 mRNA throughout the menstrual cycle. A higher mRNA level was observed in ectopic endometrium (Ec) from women with endometriosis compared with eutopic endometrium (Eu) from women with endometriosis. Immunohistochemistry revealed a varied pattern of laminin gamma 2 chain expression, with increased epithelial expression in eutopic endometrium from women with endometriosis compared with those without endometriosis. CONCLUSIONS: The altered expression of laminin gamma 2 chain in eutopic endometrium from women with endometriosis may provide new opportunities for diagnosis and treatment. [less ▲]Detailed reference viewed: 26 (5 ULg)
Hyperglycosylated human chorionic gonadotropin stimulates angiogenesis through TGF-beta receptor activation.
; Blacher, Silvia ; Munaut, Carine et al
in FASEB Journal (2013), 27(4), 1309-21
Embryo implantation requires extensive angiogenesis at the maternal-fetal interface. Hyperglycosylated human chorionic gonadotropin (hCG-H), a trophoblast invasive signal produced by extravillous ... [more ▼]
Embryo implantation requires extensive angiogenesis at the maternal-fetal interface. Hyperglycosylated human chorionic gonadotropin (hCG-H), a trophoblast invasive signal produced by extravillous cytotrophoblasts and by choriocarcinoma, was evaluated for its angiogenic role. hCG-H was purified by HPLC from choriocarcinoma supernatant, and the glycosylation pattern was determined by 2D gel analysis. Angiogenesis models used were aortic ring assay with wild-type and LHCGR-knockout mice, endothelial and mural cell proliferation, and migration assays. The TGF-beta signaling pathway was studied by coimmunoprecipitation, competitive binding, TGF-beta reporter gene assays, and Smad immunoblotting. hCG-H displayed a potent angiogenic effect [3.2-fold increase of number of vessel intersections in wild-type aortic rings (11.406 to 36.964)]. hCG-H-induced angiostimulation was independent of the classic hCG signaling pathway since it persisted in LHCGR-knockout mice [4.73-fold increase of number of vessel intersections (10.826 to 51.288)]. Using TGF-beta signaling inhibitors, Tbeta-RII was identified as the hCG-H receptor responsible for its angiogenic switch. hCG-H exposure enhanced phosphorylation of Smad 2 in endothelial and mural cells and genomic activation of Smad-responsive elements. Interaction between hCG-H and Tbeta-RII was demonstrated by coimmunoprecipitation and binding competition with (125)I-TGF-beta. This new paracrine interaction between trophoblast and endothelial cells through the hCG-H and the TGF-beta receptor complex plays a key role in angiogenesis associated with placental development and tumorigenesis. [less ▲]Detailed reference viewed: 52 (8 ULg)
Expression of type 2 orexin receptor in human endometrium and its epigenetic silencing in endometrial cancer.
Dehan, Pierre ; ; et al
in Journal of Clinical Endocrinology and Metabolism (2013), 98(4), 1549-57
CONTEXT: Orexins A and B are neuropeptides that bind and activate 2 types of receptors. In addition to direct action in the brain, the orexinergic system has broader implications in peripheral organs, and ... [more ▼]
CONTEXT: Orexins A and B are neuropeptides that bind and activate 2 types of receptors. In addition to direct action in the brain, the orexinergic system has broader implications in peripheral organs, and it has been proposed to have a role in the induction of apoptosis. There are very few data on the endometrium. OBJECTIVE: The expression and epigenetic regulation of type 2 orexin receptor (OX2R) was investigated in the human endometrium as well as in endometrial endometrioid carcinoma (EEC). METHODS: OX2R localization was studied by immunohistochemistry in normal endometrium (n = 24) and in EEC (n = 32). The DNA methylation status of a CpG island located in the first exon of OX2R was analyzed by bisulfite sequencing in normal (n = 18), EEC (n = 34), and 3 endometrial cell lines. On the latter, mRNA expression and Western blotting as well as in vitro induction with orexin were performed. RESULTS: Expression of the OX2R protein was detected in normal endometrial epithelia, whereas it was frequently lacking in EEC. This loss was associated with hypermethylation of OX2R in EEC in comparison with normal endometrium (median CpG methylation percentages of 48.85% and 5.85%, respectively). In cell lines, hypermethylation correlated with weak OX2R expression. Additionally, in vitro treatment of the 3 EEC cell lines with orexins A and B did not result in proliferation change CONCLUSIONS: Altogether our data provide evidence for the epigenetic silencing of OX2R in EEC. The implication of the OX2R loss in tumoral progression remains to be elucidated. [less ▲]Detailed reference viewed: 9 (2 ULg)
Impact of follicular G-CSF quantification on subsequent embryo transfer decisions: a proof of concept study.
; Gridelet, Virginie ; RAVET, Stéphanie et al
in Human Reproduction (2013), 28(2), 406-13
BACKGROUND: Previous experiments have shown that granulocyte colony-stimulating factor (G-CSF), quantified in the follicular fluid (FF) of individual oocytes, correlates with the potential for an ongoing ... [more ▼]
BACKGROUND: Previous experiments have shown that granulocyte colony-stimulating factor (G-CSF), quantified in the follicular fluid (FF) of individual oocytes, correlates with the potential for an ongoing pregnancy of the corresponding fertilized oocytes among selected transferred embryos. Here we present a proof of concept study aimed at evaluating the impact of including FF G-CSF quantification in the embryo transfer decisions. METHODS: FF G-CSF was quantified with the Luminex XMap technology in 523 individual FF samples corresponding to 116 fresh transferred embryos, 275 frozen embryos and 131 destroyed embryos from 78 patients undergoing ICSI. RESULTS: Follicular G-CSF was highly predictive of subsequent implantation. The receiving operator characteristics curve methodology showed its higher discriminatory power to predict ongoing pregnancy in multivariate logistic regression analysis for FF G-CSF compared with embryo morphology [0.77 (0.69-0.83), P < 0.001 versus 0.66 (0.58-0.73), P = 0.01)]. Embryos were classified by their FF G-CSF concentration: Class I over 30 pg/ml (a highest positive predictive value for implantation), Class II from 30 to 18.4 pg/ml and Class III <18.4 pg/ml (a highest negative predictive value). Embryos derived from Class I follicles had a significantly higher implantation rate (IR) than those from Class II and III follicles (36 versus 16.6 and 6%, P < 0.001). Embryos derived from Class I follicles with an optimal morphology reached an IR of 54%. Frozen-thawed embryos transfer derived from Class I follicles had an IR of 37% significantly higher than those from Class II and III follicles, respectively, of 8 and 5% (P < 0.001). Thirty-five per cent of the frozen embryos but also 10% of the destroyed embryos were derived from G-CSF Class I follicles. Non-optimal embryos appear to have been transferred in 28% (22/78) of the women, and their pregnancy rate was significantly lower than that of women who received at least one optimal embryo (18 versus 36%, P = 0.04). CONCLUSIONS: Monitoring FF G-CSF for the selection of embryos with a better potential for pregnancy might improve the effectiveness of IVF by reducing the time and cost required for obtaining a pregnancy. [less ▲]Detailed reference viewed: 61 (8 ULg)
Use of Sheep Ovarian Tissue as a Model to Restore Fertility in Young Cancerous Women
Fransolet, Maïté ; HENRY, Laurie ; Rozet, Eric et al
Poster (2012, December 10)Detailed reference viewed: 65 (15 ULg)
Expression et localisation spatio-temporelle de KISS1 et de son récepteur KISSR dans le placenta normal et pathologique.
VALDES SOCIN, Hernan Gonzalo ; Munaut, Carine ; CHAVEZ, Viviana et al
Poster (2012, October)
Objectif : Etudier l’expression de KISS1 (métastatine) et de son récepteur KISS1R lors de la grossesse normale et pathologique. Matériels et méthodes : Nous avons étudié la localisation de KISS1 et KISS1R ... [more ▼]
Objectif : Etudier l’expression de KISS1 (métastatine) et de son récepteur KISS1R lors de la grossesse normale et pathologique. Matériels et méthodes : Nous avons étudié la localisation de KISS1 et KISS1R par immunohistochimie dans des placentas normaux (1 er et 3 ème trimestre). Par RT-PCR quantitative, nous avons évalué le niveau d’expression des ARNm dans les placentas et les lits placentaires correspondants. Les niveaux d’expression de ARNm ont été comparés entre les grossesses normales (GN, n=13) et les grossesses spathologiques Prééclampsiques -PE-, n=17 et retard de croissance intrautérine -RCIU-, n=9). Résultats : Au premier trimestre des GN, KISS1 est majoritairement localisé dans les syncitiotrophoblastes, alors que KISS1R est détecté dans le mesenchyme villositaire. Au cours du troisième trimestre, KISS1 est uniquement localisé dans le syncitiotrophoblaste au contact avec la décidue et dans le mésenchyme villositaire et KISS1R est détecté dans le trophoblaste extra-villeux ainsi que dans quelques cellules de la décidue. Les analyses par RT-PCR mettent en évidence une expression plus importante des ARNm de KISS1 (p<0,001) et de KISS1R (p=0.039) dans les placentas (GN,PE et RCIU) par rapport aux lits placentaires correspondants. Les niveaux d’expression de KISS1 et KISS1R ne sont pas, cependant, significativement modulés dans les grossesses pathologiques. Conclusions : Par immunohistochimie, nos résultats indiquent une expression spatiotemporelle différente pour KISS1 et KISS1R entre le 1 er et 3 ème trimestre des grossesses normales. Nous n’avons pas mis en évidence de modulation de l’expression des ARNm dans les grossesses pathologiques. [less ▲]Detailed reference viewed: 42 (9 ULg)
The actors of human implantation: gametes, embryo and endometrium
Gridelet, Virginie ; GASPARD, Olivier ; Polese, Barbara et al
in Violin Pereira, Luis Antonio (Ed.) Embryology - Updates and Highlights on Classic Topics (2012)Detailed reference viewed: 34 (7 ULg)
Differential expression of Vegfr-2 and its soluble form in preeclampsia.
Munaut, Carine ; LORQUET, Sophie ; Pequeux, Christel et al
in PLoS ONE (2012), 7(3), 33475
Background: Several studies have suggested that the main features of preeclampsia (PE) are consequences of endothelial dysfunction related to excess circulating anti-angiogenic factors, most notably ... [more ▼]
Background: Several studies have suggested that the main features of preeclampsia (PE) are consequences of endothelial dysfunction related to excess circulating anti-angiogenic factors, most notably, soluble sVEGFR-1 (also known as sFlt-1) and soluble endoglin (sEng), as well as to decreased PlGF. Recently, soluble VEGF type 2 receptor (sVEGFR-2) has emerged as a crucial regulator of lymphangiogenesis. To date, however, there is a paucity of information on the changes of VEGFR-2 that occur during the clinical onset of PE. Therefore, the aim of our study was to characterize the plasma levels of VEGFR-2 in PE patients and to perform VEGFR-2 immunolocalization in placenta. METHODOLOGY/PRINCIPAL FINDINGS: By ELISA, we observed that the VEGFR-2 plasma levels were reduced during PE compared with normal gestational age matched pregnancies, whereas the VEGFR-1 and Eng plasma levels were increased. The dramatic drop in the VEGFR-1 levels shortly after delivery confirmed its placental origin. In contrast, the plasma levels of Eng and VEGFR-2 decreased only moderately during the early postpartum period. An RT-PCR analysis showed that the relative levels of VEGFR-1, sVEGFR-1 and Eng mRNA were increased in the placentas of women with severe PE. The relative levels of VEGFR-2 mRNA as well as expressing cells, were similar in both groups. We also made the novel finding that a recently described alternatively spliced VEGFR-2 mRNA variant was present at lower relative levels in the preeclamptic placentas. CONCLUSIONS/SIGNIFICANCE: Our results indicate that the plasma levels of anti-angiogenic factors, particularly VEGFR-1 and VEGFR-2, behave in different ways after delivery. The rapid decrease in plasma VEGFR-1 levels appears to be a consequence of the delivery of the placenta. The persistent circulating levels of VEGFR-2 suggest a maternal endothelial origin of this peptide. The decreased VEGFR-2 plasma levels in preeclamptic women may serve as a marker of endothelial dysfunction. [less ▲]Detailed reference viewed: 54 (7 ULg)
Characterization of synovial angiogenesis in osteoarthritis patients and its modulation by chondroitin sulfate
Lambert, Cécile ; ; et al
in Arthritis Research & Therapy (2012), 14(2), 58
INTRODUCTION: This work aimed at comparing the production of inflammatory and pro- and anti-angiogenic factors by normal/reactive (N/R) or inflammatory (I) areas of the osteoarthritic synovial membrane ... [more ▼]
INTRODUCTION: This work aimed at comparing the production of inflammatory and pro- and anti-angiogenic factors by normal/reactive (N/R) or inflammatory (I) areas of the osteoarthritic synovial membrane. The effects of interleukin (IL)-1β and chondroitin sulfate (CS) on the expression of pro- and anti-angiogenic factors by synovial fibroblasts cells (SFC) were also studied. METHODS: Biopsies from N/R or from I areas of osteoarthritic synovial membrane were collected at the time of surgery. The inflammatory status of the synovial membrane was characterized by the surgeon according to macroscopic criteria, including the synovial vascularization, the villi formation and the hypertrophic aspect of the tissue. We assessed the expression of CD45, von Willebrand factor and vascular endothelial growth factor (VEGF) antigen by immunohistochemistry in both N/R and I biopsies. The production of IL-6, -8, VEGF and thrombospondin (TSP)-1 by N/R or I synovial cells was quantified by ELISA. SFC were cultured in the absence or in the presence of IL-1β (1 ng/ml) and with or without CS (10, 50, 200 μg/ml). Gene expression of pro-angiogenic factors (VEGF, basic fibroblast growth factor (bFGF), nerve growth factor (NGF), matrix metalloproteinase (MMP)-2 and angiopoietin (ang)-1) and anti-angiogenic factors (vascular endothelial growth inhibitor (VEGI), TSP-1 and -2) were determined by real time RT-PCR. Production of VEGI and TSP-1 was also estimated by ELISA. RESULTS: Immunohistochemistry showed the increase of lymphocyte infiltration, vascular density and VEGF expression in I compared to N/R synovial biopsies. Synovial cells from I areas produced more IL-6, IL-8 and VEGF but less TSP-1 than cells isolated from N/R synovial biopsies. The expression of pro-angiogenic factors by SFC was stimulated by IL-1β. A time dependent regulation of the expression of anti-angiogenic factor genes was observed. IL-1β stimulated the expression of anti-angiogenic factor genes but inhibited it after 24 h. CS reversed the inhibitory effect of IL-1β on anti-angiogenic factors, VEGI and TSP-1. CONCLUSIONS: We demonstrated that synovial biopsies from I areas expressed a pro-angiogenic phenotype. IL-1β induced an imbalance between pro- and anti-angiogenic factors in SFC and CS tended to normalize this IL-1β-induced imbalance, providing a new possible mechanism of action of this drug. [less ▲]Detailed reference viewed: 34 (11 ULg)
Does vascular endothelial growth factor improve ovarian tissue recovery after cryopreservation?
Henry, Laurie ; Fransolet, Maïté ; Labied, Soraya et al
in Giornale italiano di obstetricia e gynecologia (2012)Detailed reference viewed: 36 (7 ULg)
Isoform 111 of vascular endothelial growth factor (VEGF111) improves angiogenesis of ovarian tissue xenotransplantation
Labied, Soraya ; Delforge, Yves ; Blacher, Silvia et al
in Journal of Assisted Reproduction & Genetics (2012), 28(11), 1009Detailed reference viewed: 38 (15 ULg)
The proteolytic activity of MT4-MMP is required for its proangiogenic and pro-metastatic promoting effects
; Paye, Alexandra ; Detry, Benoît et al
in International Journal of Cancer = Journal International du Cancer (2012), 131(7), 1537-1548
MT4-MMP expression in breast adenocarcinoma stimulates tumor growth and metastatic spreading to the lung. However whether these pro-tumorigenic and pro-metastatic effects of MT4-MMP are related to a ... [more ▼]
MT4-MMP expression in breast adenocarcinoma stimulates tumor growth and metastatic spreading to the lung. However whether these pro-tumorigenic and pro-metastatic effects of MT4-MMP are related to a proteolytic action is not known yet. Through site directed mutagenesis MT4-MMP has been inactivated in cancer cells through Glutamic acid 249 substitution by Alanine in the active site. Active MT4-MMP triggered an angiogenic switch at day 7 after tumor implantation and drastically accelerated subcutaneous tumor growth as well as lung colonization in RAG -/- mice. All these effects were abrogated upon MT4-MMP inactivation. In sharp contrast to most MMPs being primarily of stromal origin, we provide evidence that tumor-derived MT4-MMP, but not host-derived MT4-MMP contributes to angiogenesis. A genetic approach using MT4-MMP-deficient mice revealed that the status of MT4-MMP produced by host cells did not affect the angiogenic response. Despite of this tumor intrinsic feature, to exert its tumor promoting effect, MT4-MMP requires a permissive microenvironment. Indeed, tumor-derived MT4-MMP failed to circumvent the lack of an host angio-promoting factor such as lasminogen activator inhibitor (PAI-1). Overall, our study demonstrates the key contribution of MT4-MMP catalytic activity in the tumor compartment, at the interface with host cells. It identifies MT4-MMP as a key intrinsic tumor cell determinant that contributes to the elaboration of a permissive microenvironment for metastatic dissemination [less ▲]Detailed reference viewed: 74 (14 ULg)
Abnormal vascular architecture at the placental-maternal interface in placenta increta
CHANTRAINE, Frédéric ; Blacher, Silvia ; et al
in American Journal of Obstetrics and Gynecology (2012), 207(3), 1881-9
Objective The objective of the study was to characterize the vascular architecture at the placental-maternal interface in pregnancies complicated by placenta increta and normal pregnancies. Study Design ... [more ▼]
Objective The objective of the study was to characterize the vascular architecture at the placental-maternal interface in pregnancies complicated by placenta increta and normal pregnancies. Study Design Vessel numbers and cross-section area density and spatial and area distributions in 13 placenta-increta placental beds were compared with 9 normal placental beds using computer-assisted image analysis of whole-slide CD31 immunolabeled sections. Results The total areas occupied by vessels in normal and placenta-increta placental beds were comparable, but vessels were significantly sparser and larger in the latter. Moreover, placenta-increta–vessel distributions (area and distance from the placental–myometrial junction) were more heterogeneous. Conclusion Size and spatial organization of the placenta-increta vascular architecture at the placental-maternal interface differed from normal and might partially explain the severe hemorrhage observed during placenta-increta deliveries. [less ▲]Detailed reference viewed: 30 (12 ULg)
TGFbeta-receptor-dependent angiostimulation through the hyperglycosylated isoform of human chorionic gonadotropin.
; ; et al
in Placenta (2011), 32(9), 44Detailed reference viewed: 6 (0 ULg)
Transient reduction of placental angiogenesis in PAI-1 deficient mice
Labied, Soraya ; Blacher, Silvia ; et al
in Physiological Genomics (2011), 43(4), 188-98
Murine placentation is associated with the invasion of maternal endometrium by trophoblasts and an extensive maternal and foetal angiogenesis. Plasminogen activator inhibitor-1 (PAI-1) is transiently ... [more ▼]
Murine placentation is associated with the invasion of maternal endometrium by trophoblasts and an extensive maternal and foetal angiogenesis. Plasminogen activator inhibitor-1 (PAI-1) is transiently produced by spongiotrophoblasts and trophoblast giant cells at 10.5-11.5 day post-coitum (dpc). Knowing the key contribution of PAI-1 in the regulation of angiogenesis, we have now analyzed the consequence of PAI-1 deficiency on murine placentation. Morphological and quantitative computer-assisted image analysis revealed abnormal placental morphology in PAI-1 (-/-) mice at 10.5 and 12.5 dpc. At 10.5 dpc, the genetic ablation of PAI-1 resulted in a transient reduction of both maternal and foetal vascularizations in the placenta and increased trophoblast cell density. This was associated with a poorer development of the labyrinth and an extension of the decidua. A larger spongiotrophoblast layer appeared at 12.5 dpc in PAI-1 deficient mice. Placental morphology was normalized at 14,5 dpc. Microarray analyses performed on laser capture microdissected labyrinths revealed that 46 genes were differentially expressed at 10.5 dpc between the two genotypes. However, only 11 genes were still differently modulated at 14.5 dpc when normalization of placental morphology had take place. This transcriptomic profiling highlighted a dysregulation in the expression of placenta-related cathepsin family members. All together our data provide evidence for a transient impaired placental morphology in PAI-1-deficient mice which is then normalized leading to normal embryonic development. [less ▲]Detailed reference viewed: 80 (13 ULg)
Whole Slide Quantification of Stromal Lymphatic Vessel Distribution and Peritumoral Lymphatic Vessel Density in Early Invasive Cervical Cancer: A Method Description
Balsat, Cédric ; Blacher, Silvia ; et al
in ISRN Obstetrics and Gynecology (2011), 2011
Peritumoral Lymphatic Vessel Density (LVD) is considered to be a predictive marker for the presence of lymph node metastases in cervical cancer. However, when LVD quantification relies on conventional ... [more ▼]
Peritumoral Lymphatic Vessel Density (LVD) is considered to be a predictive marker for the presence of lymph node metastases in cervical cancer. However, when LVD quantification relies on conventional optical microscopy and the hot spot technique, interobserver variability is significant and yields inconsistent conclusions. In this work, we describe an original method that applies computed image analysis to whole slide scanned tissue sections following immunohistochemical lymphatic vessel staining. This procedure allows to determine an objective LVD quantification as well as the lymphatic vessel distribution and its heterogeneity within the stroma surrounding the invasive tumor bundles. The proposed technique can be useful to better characterize lymphatic vessel interactions with tumor cells and could potentially impact on prognosis and therapeutic decisions. [less ▲]Detailed reference viewed: 94 (16 ULg)
Does isoforms 111 and 165 of vascular endothelial growth factor (VEGF111 and 165) improve transplanted ovarian tissue survival?
Henry, Laurie ; Fransolet, Maïté ; LABIED, Soraya et al
in Journal of Assisted Reproduction & Genetics (2011), 28Detailed reference viewed: 37 (14 ULg)
Bone marrow-derived mesenchymal cells and MMP13 contribute to experimental choroidal neovascularization.
Lecomte, Julie ; ; Detry, Benoît et al
in Cellular and Molecular Life Sciences : CMLS (2011), 68
In this study, we evaluate the potential involvement of collagenase-3 (MMP13), a matrix metalloproteinase (MMP) family member, in the exudative form of age-related macular degeneration characterized by a ... [more ▼]
In this study, we evaluate the potential involvement of collagenase-3 (MMP13), a matrix metalloproteinase (MMP) family member, in the exudative form of age-related macular degeneration characterized by a neovascularisation into the choroid. RT-PCR analysis revealed that human neovascular membranes issued from patients with AMD expressed high levels of Mmp13. The contribution of MMP13 in choroidal neovascularization (CNV) formation was explored by using a murine model of laser-induced CNV and applying it to wild-type mice (WT) and Mmp13-deficient mice (Mmp13 ( -/- ) mice). Angiogenic and inflammatory reactions were explored by immunohistochemistry. The implication of bone marrow (BM)-derived cells was determined by BM engraftment into irradiated mice and by injecting mesenchymal stem cells (MSC) isolated from WT BM. The deficiency of Mmp13 impaired CNV formation which was fully restored by WT BM engraftment and partially rescued by several injections of WT MSC. The present study sheds light on a novel function of MMP13 during BM-dependent choroidal vascularization and provides evidence for a role for MSC in the pathogenesis of CNV. [less ▲]Detailed reference viewed: 136 (31 ULg)
New pre-conception immune biomarkers for clinical practice: interleukin-18, interleukin-15 and TWEAK on the endometrial side, G-CSF on the follicular side.
; ; et al
in Journal of Reproductive Immunology (2011), 88(2), 118-123
dentification of biomarkers of optimal uterine receptivity to the implanting embryo as well as biomarkers of oocyte competence would undoubtedly improve the efficiency of assisted reproductive technology ... [more ▼]
dentification of biomarkers of optimal uterine receptivity to the implanting embryo as well as biomarkers of oocyte competence would undoubtedly improve the efficiency of assisted reproductive technology (ART). Expression of IL-15 and IL-18 has been shown to be different in patients with failed implantation after IVF/ICSI compared with fertile controls and both correlate with local uNK (CD56+) recruitment and angiogenesis. Tumor necrosis factor weak inducer of apoptosis (TWEAK) has been described in mice as a potent early immune regulator able to protect the conceptus. The results of our studies in human suggest that TWEAK modulates the IL-18 related cytotoxicity of uNK cells. Quantification of IL-18, TWEAK and IL-15 mRNA expression by real-time PCR in endometrial tissue collected in mid-luteal phase of non-conception cycles allowed documentation of physiological events that occur at the time of uterine receptivity. Such information may be useful for the physician especially in patients where embryos fail to implant. Cytokine quantification may assist in understanding the mechanisms leading to repeated IVF/ICSI failure: either depletion of cytokines necessary for the apposition-adhesion, or an excess of cytokines leading to local cytotoxicity, may impair the implantation of the embryo. Other new data suggest that a pre-conception dialogue mediated by the oocyte and the follicular fluid and the oocyte may contribute to later implantation success. Follicular concentration of G-CSF appears as a useful biomarker of oocyte competence before fertilization. Moreover both in human and animal models, evidence of a role of the endometrium as a biosensor of the embryo is emerging. [less ▲]Detailed reference viewed: 65 (15 ULg)
Specific and extensive endometrial deregulation is present before conception in IVF/ICSI repeated implantation failures (IF) or recurrent miscarriages.
; Munaut, Carine ; et al
in Journal of Pathology (The) (2011), 225(4), 554-64
The objective was to examine if IVF/ICSI repeated implantation failures (IF) or recurrent miscarriages (RM) could be related to preconceptional endometrial deregulations. IF was defined as the absence of ... [more ▼]
The objective was to examine if IVF/ICSI repeated implantation failures (IF) or recurrent miscarriages (RM) could be related to preconceptional endometrial deregulations. IF was defined as the absence of pregnancy despite the transfer of at least ten IVF/ICSI good quality embryos, and RM as having at least three unexplained miscarriages. Fertile controls (FC) were women who had given birth at least once. Endometrial biopsy was performed in the mild luteal phase of a non-conceptual cycle (five women were selected in each group). Affymetrix chips (GeneChip Human Genome U133 Plus2.0 Array) were used for hybridization. Data were normalized by the gcRMA method, and raw p values adjusted by the Bonferroni procedure (1%). Differential expression of selected genes was analysed using real-time PCR. Gene networks and biological functions were explored using the Ingenuity Pathways Analysis software. Endometrial gene expression profiles at the time of uterine receptivity differ dramatically in the endometrium among FC, RM, and IF patients. Compared to FC, 2126 and 2477 genes are differentially expressed in IF and RM groups, respectively, and 2363 between IF and RM. In both conditions, differential gene expression referred mainly to DNA transcription and expression. Other main cellular functions deregulated in IF conditions correspond to cell morphology, cellular development, cell cycle, and cellular assembly, while in RM conditions, deregulated cellular functions relate to cell signalling (degradation of cyclic AMP and calcium metabolism) and cellular maintenance. In both conditions, there is an over-representation of deregulations related to the haematological system. In the IF condition, cell-mediated immune response and nervous system development and function are highly deregulated, while in RM patients, main deregulations are in organ and tissue development, humoral immune response, and muscular system development and function. Extensive endometrial deregulations are present before conception in patients who experienced IF or RM with both distinct and common deregulation. [less ▲]Detailed reference viewed: 21 (2 ULg)