scholarly journals 014.Novel uterine genes in regulation of embryo implantation

2004 ◽  
Vol 16 (9) ◽  
pp. 14
Author(s):  
G. Nie ◽  
Y. Li ◽  
K. Luu ◽  
J. Findlay ◽  
L. Salamonsen
Keyword(s):  
Antisense Oligonucleotides ◽  
Embryo Implantation ◽  
Uterine Receptivity ◽  
Temporal Expression ◽  
Tissue Remodelling ◽  
Functional Studies ◽  
Molecular Events ◽  
Uterine Environment ◽  
Identity Expression

Implantation of the embryo into the maternal endometrium is the first and critical step leading to the establishment of a pregnancy. It has been well established that only during the 'window' of implantation, a limited time span when the uterine environment is receptive, can a blastocyst successfully implant into the uterus. The development of uterine receptivity is accompanied by remarkable morphological and physiological changes in the endometrium, and this is primarily driven by the coordinated effects of the ovarian steroid hormones. Uterine tissue remodelling during implantation also contributes significantly to the development of the placenta. Insufficient uterine remodelling causes implantation failure and infertility. To date, the exact molecular events occurring in the uterus during the establishment of receptivity and at the actual site of implantation are still not well understood. We used the mouse as a model and identified a number of previously unrecognised molecules that are uniquely regulated in the early stages of implantation: one of these is proprotein convertase 6 (PC6). The potential importance of these genes and their products in modulating fertility in the primate, including the human, was demonstrated by their unique spatial and temporal expression in the endometrium of human and rhesus monkey during the phase of uterine receptivity and at implantation. The importance of the genes for implantation was ultimately confirmed by functional studies in vivo using morpholino antisense oligonucleotides. These molecules will be discussed in terms of their identity, expression and functions.

scholarly journals Potential ligand-receptor-pathway cascades and a novel non-metabolic function of lactate in remodeling uterine receptivity by inducing endometrial histone lactylation at implantation, revealed by a proteomic atlas of maternal-fetal crosstalk

2021 ◽  
Author(s):  
Qianying Yang ◽  
Juan Liu ◽  
Yue Wang ◽  
Wei Zhao ◽  
Wenjing Wang ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
Redox Homeostasis ◽  
Integrated Analysis ◽  
Physical Interaction ◽  
Metabolic Function ◽  
Uterine Receptivity ◽  
Cellular Mechanisms ◽  
Receptor Complexes

Abstract Well-orchestrated maternal-fetal crosstalk involves secreted ligands, interacting receptors, and coupled pathways between the conceptus and endometrium. However, previous researches mainly focused on either the conceptus or endometrium in isolation. The lack of integrated analysis, especially on protein levels, has made it challenging to advance our understanding of the crosstalk. Herein, focusing on ligand–receptor complexes and coupled pathways at maternal-fetal interface in sheep, a well-established embryo implantation model, we provide the first comprehensive proteomic atlas of ligand-receptor-pathway cascades that may be essential for implantation. Based on these candidate interactions, we further revealed the physical interaction of albumin-claudin 4 and their role in facilitating embryo attachment to endometrium. More interestingly, we demonstrated a novel non-metabolic function of enhanced conceptus glycolysis in remodeling uterine receptivity, by inducing endometrial histone lactylation, a newly identified histone modification. Our results from in vitro and in vivo models supported the essential role of lactate, as a key embryonic signal, in regulating redox homeostasis and apoptotic balance to ensure successful implantation. Our study identified many putative molecular and cellular mechanisms that fine-tuned conceptus-endometrium crosstalk during implantation, thus providing important clues for developing potential clinical intervention strategies to improve pregnancy outcomes following both natural conception and assisted reproduction.

155. UNDERSTANDING THE CROSSTALK IN THE HUMAN UTERINE CAVITY: ROLES FOR SOLUBLE MEDIATORS DURING EMBRYO IMPLANTATION

2010 ◽  
Vol 22 (9) ◽  
pp. 73
Author(s):  
N. Hannan ◽  
P. Paiva ◽  
K. L. Meehan ◽  
C. Hincks ◽  
L. J. F. Rombauts ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Embryo Implantation ◽  
Uterine Cavity ◽  
Uterine Receptivity ◽  
Adhesive Properties ◽  
Infertile Women ◽  
Functional Studies ◽  
Glandular Secretion ◽  
Uterine Fluid ◽  
Insight Into

Embryo implantation requires synchronized dialogue between a receptive endometrium and an activated blastocyst via locally produced soluble mediators. During the mid-secretory (MS) phase of the menstrual cycle there is increased glandular secretion into the uterine lumen. These secretions contain important mediators that modulate the endometrium and support the conceptus during implantation. Analysis of the composition of uterine fluid across the menstrual cycle and in fertile and infertile women will, therefore, provide new insights into uterine receptivity. We hypothesized that multiplex platform analysis of human uterine lavages would identify soluble mediators important for the establishment of pregnancy in humans. Lavages were collected (by flushing the uterine cavity with 5mL of saline) from fertile and infertile women during the MS phase and from fertile women during the mid-proliferative (MP) phase of the menstrual cycle. Comparison of lavages from the three cohorts was performed using quantitative MilliplexTM Luminex® cytokine/chemokine assays containing 42-analytes. Luminex analysis detected a number of cytokines in uterine fluid, revealing 8 soluble mediators previously unknown in the endometrium and present in human uterine fluid including, PDGF-AA, TNFβ, sIL-2Rα, Flt-3 ligand, sCD40L, IL-7, IFNα2 and GRO. Furthermore comparison of the three cohorts revealed VEGF levels were significantly higher in the fertile (MS) fluid when compared to infertile. Functional studies demonstrated that rhVEGF treatment significantly increased the adhesive properties in cells present at the maternal-fetal interface. These findings suggest VEGF plays a role in regulating embryo implantation. Furthermore identifying the soluble mediators in uterine fluid may provide potential markers of endometrial receptivity, insight into the unique microenvironment essential for pregnancy and a profile of maternal factors that influence the implanting blastocyst.

scholarly journals Regulation of ARHGAP19 in the endometrial epithelium: a possible role in the establishment of uterine receptivity

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jingjie Liang ◽  
Kui Li ◽  
Kaiyu Chen ◽  
Junyong Liang ◽  
Ti Qin ◽  
...  
Keyword(s):  
Rho Gtpase ◽  
Embryo Implantation ◽  
Luciferase Assay ◽  
Uterine Receptivity ◽  
Morphological Transformation ◽  
Upstream Regulator ◽  
Junctional Proteins

Abstract Background The establishment of uterine receptivity is essential for embryo implantation initiation and involves a significant morphological transformation in the endometrial epithelial cells (EECs). The remodeling of junctional complexes and membrane-associated cytoskeleton is crucial for epithelial transformation. However, little is known about how this process is regulated in EECs during the receptive phase. ARHGAP19 is a Rho GTPase-activating protein that participates in various cytoskeletal-related events, including epithelial morphogenesis. Here, we investigated the role of ARHGAP19 in endometrial epithelial transformation during the establishment of uterine receptivity. The upstream regulator of ARHGAP19 was also investigated. Methods ARHGAP19 expression was examined in mouse uteri during early pregnancy and in human EEC lines. The role of ARHGAP19 was investigated by manipulating its expression in EECs. The effect of ARHGAP19 on junctional proteins in EECs was examined by western blotting and immunofluorescence. The effect of ARHGAP19 on microvilli was examined by scanning electron microscopy. The upstream microRNA (miRNA) was predicted using online databases and validated by the dual-luciferase assay. The in vivo and in vitro effect of miRNA on endogenous ARHGAP19 was examined by uterine injection of miRNA agomirs and transfection of miRNA mimics or inhibitors. Results ARHGAP19 was upregulated in the receptive mouse uteri and human EECs. Overexpression of ARHGAP19 in non-receptive EECs downregulated the expression of junctional proteins and resulted in their redistribution. Meanwhile, upregulating ARHGAP19 reorganized the cytoskeletal structure of EECs, leading to a decline of microvilli and changes in cell configuration. These changes weakened epithelial cell polarity and promoted the transition of non-receptive EECs to a receptive phenotype. Besides, miR-192-5p, a miRNA that plays a key role in maintaining epithelial properties, was validated as an upstream regulator of ARHGAP19. Conclusion These results suggested that ARHGAP19 may contribute to the transition of EECs from a non-receptive to a receptive state by regulating the remodeling of junctional proteins and membrane-associated cytoskeleton.

scholarly journals miR-183-5p regulates uterine receptivity and enhances embryo implantation

2020 ◽  
Vol 64 (1) ◽  
pp. 43-52 ◽  
Author(s):  
Rubab Akbar ◽  
Kamran Ullah ◽  
Tanzil Ur Rahman ◽  
Yi Cheng ◽  
Hai-Yan Pang ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Luciferase Reporter ◽  
Uterine Receptivity ◽  
Positive Role ◽  
Endometrial Cells ◽  
Estrogenic Effects ◽  
Reporter Assays ◽  
Downstream Analysis

Receptive endometrium is a prerequisite for successful embryo implantation, and it follows that poor endometrial receptivity is a leading cause of implantation failure. miRNAs play important roles as epigenetic regulators of endometrial receptivity and embryo implantation through post-transcriptional modifications. However, the mechanisms of action of many miRNAs are poorly understood. In this study, we investigated the role of the miR-183 family, comprising three miRNAs (miR-183-5p, miR-182-5p, and miR-96-5p) in endometrial receptivity and embryo implantation. The miR-183 family shows estrogen-dependent upregulation in endometrial Ishikawa (IK) cells. The miR-183 family also has a positive role in migration and proliferation of IK cells. Furthermore, JAr spheroid attachment experiments show that attachment rates were significantly decreased after treatment of IK cells with inhibitors for miR-183-5p and miR-182-5p and increased after treatment with miR-183-5p-mimic and miR-96-5p-mimic, respectively. The downstream analysis shows that catenin alpha 2 (CTNNA2) is a potential target gene for miR-183-5p, and this was confirmed in luciferase reporter assays. An in vivo mouse pregnancy model shows that inhibition of miR-183-5p significantly decreases embryo implantation rates and increases CTNNA2 expression. Downregulation of CTNNA2 in endometrial cells by miR-183-5p may be significant in mediating estrogenic effects on endometrial receptivity. In conclusion, miR-183-5p and the CTNNA2 gene may be potential biomarkers for endometrial receptivity and may be useful diagnostic and therapeutic targets for successful embryo implantation.

scholarly journals Regulation of ARHGAP19 in the endometrial epithelium: a possible role in the establishment of uterine receptivity

2020 ◽  
Author(s):  
Jingjie Liang ◽  
Kui Li ◽  
Kaiyu Chen ◽  
Junyong Liang ◽  
Ti Qin ◽  
...  
Keyword(s):  
Rho Gtpase ◽  
Embryo Implantation ◽  
Luciferase Assay ◽  
Uterine Receptivity ◽  
Morphological Transformation ◽  
Upstream Regulator ◽  
Junctional Proteins

Abstract Background: The establishment of uterine receptivity is essential for embryo implantation initiation and involves a significant morphological transformation in the endometrial epithelial cells (EECs). The remodeling of junctional complexes and membrane-associated cytoskeleton is crucial for epithelial transformation. However, little is known about how this process is regulated in EECs during the receptive phase. ARHGAP19 is a Rho GTPase-activating protein that participates in various cytoskeletal-related events, including epithelial morphogenesis. Here, we investigated the role of ARHGAP19 in endometrial epithelial transformation during the establishment of uterine receptivity. The upstream regulator of ARHGAP19 was also investigated. Methods: ARHGAP19 expression was examined in mouse uteri during early pregnancy and in human EEC lines. The role of ARHGAP19 was investigated by manipulating its expression in EECs. The effect of ARHGAP19 on junctional proteins in EECs was examined by western blotting and immunofluorescence. The effect of ARHGAP19 on microvilli was examined by scanning electron microscopy. The upstream microRNA (miRNA) was predicted using online databases and validated by the dual-luciferase assay. The in vivo and in vitro effect of miRNA on endogenous ARHGAP19 was examined by uterine injection of miRNA agomirs and transfection of miRNA mimics or inhibitors. Results: ARHGAP19 was upregulated in the receptive mouse uteri and human EECs. Overexpression of ARHGAP19 in non-receptive EECs downregulated the expression of junctional proteins and resulted in their redistribution. Meanwhile, upregulating ARHGAP19 reorganized the cytoskeletal structure of EECs, leading to a decline of microvilli and changes in cell configuration. These changes weakened epithelial cell polarity and promoted the transition of non-receptive EECs to a receptive phenotype. Besides, miR-192-5p, a miRNA that plays a key role in maintaining epithelial properties, was validated as an upstream regulator of ARHGAP19.Conclusion: These results suggested that ARHGAP19 may contribute to the transition of EECs from a non-receptive to a receptive state by regulating the remodeling of junctional proteins and membrane-associated cytoskeleton.

scholarly journals Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms

2019 ◽  
Vol 21 (1) ◽  
pp. 300 ◽  
Author(s):  
Luiz Gustavo de Almeida Chuffa ◽  
Luiz Antonio Lupi ◽  
Maira Smaniotto Cucielo ◽  
Henrique Spaulonci Silveira ◽  
Russel J. Reiter ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cell Damage ◽  
Embryo Implantation ◽  
Uterine Receptivity ◽  
Female Reproduction ◽  
Endometrial Polyps ◽  
Physiological Processes ◽  
Normal Physiological Function

The development of the endometrium is a cyclic event tightly regulated by hormones and growth factors to coordinate the menstrual cycle while promoting a suitable microenvironment for embryo implantation during the “receptivity window”. Many women experience uterine failures that hamper the success of conception, such as endometrium thickness, endometriosis, luteal phase defects, endometrial polyps, adenomyosis, viral infection, and even endometrial cancer; most of these disturbances involve changes in endocrine components or cell damage. The emerging evidence has proven that circadian rhythm deregulation followed by low circulating melatonin is associated with low implantation rates and difficulties to maintain pregnancy. Given that melatonin is a circadian-regulating hormone also involved in the maintenance of uterine homeostasis through regulation of numerous pathways associated with uterine receptivity and gestation, the success of female reproduction may be dependent on the levels and activity of uterine and placental melatonin. Based on the fact that irregular production of maternal and placental melatonin is related to recurrent spontaneous abortion and maternal/fetal disturbances, melatonin replacement may offer an excellent opportunity to restore normal physiological function of the affected tissues. By alleviating oxidative damage in the placenta, melatonin favors nutrient transfer and improves vascular dynamics at the uterine–placental interface. This review focuses on the main in vivo and in vitro functions of melatonin on uterine physiological processes, such as decidualization and implantation, and also on the feto-maternal tissues, and reviews how exogenous melatonin functions from a mechanistic standpoint to preserve the organ health. New insights on the potential signaling pathways whereby melatonin resists preeclampsia and endometriosis are further emphasized in this review.

Stem Cell Cure for Kidney Injury: Therapy to Solve Most Complex Issues in Renal System

2020 ◽  
Author(s):  
Prithiv K R Kumar
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Kidney Injury ◽  
Cell Types ◽  
Tissue Remodelling ◽  
Major Health Problem ◽  
In Vivo Experiments ◽  
Renal Regeneration ◽  
Induced Pluripotent

Renal failure is a major health problem. The mortality rate remain high despite of several therapies. The most complex of the renal issues are solved through stem cells. In this review, different mechanism for cure of chronic kidney injury along with cell engraftment incorporated into renal structures will be analysed. Paracrine activities of embryonic or induced Pluripotent stem cells are explored on the basis of stem cell-induced kidney regeneration. Several experiments have been conducted to advance stem cells to ensure the restoration of renal functions. More vigour and organised protocols for delivering stem cells is a possibility for advancement in treatment of renal disease. Also there is a need for pressing therapies to replicate the tissue remodelling and cellular repair processes suitable for renal organs. Stem cells are the undifferentiated cells that have the ability to multiply into several cell types. In vivo experiments on animal’s stem cells have shown significant improvements in the renal regeneration and functions of organs. Nevertheless more studies show several improvements in the kidney repair due to stem cell regeneration.

scholarly journals Genome wide effects of oleic acid on cultured bovine granulosa cells: evidence for the activation of pathways favoring folliculo-luteal transition

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Vengala Rao Yenuganti ◽  
Dirk Koczan ◽  
Jens Vanselow
Keyword(s):  
Oleic Acid ◽  
Granulosa Cells ◽  
System Development ◽  
Circulatory System ◽  
Bioinformatic Analysis ◽  
Negative Energy ◽  
Tissue Remodelling ◽  
Gonadotropin Secretion ◽  
Genome Wide

Abstract Background Metabolic stress, as negative energy balance on one hand or obesity on the other hand can lead to increased levels of free fatty acids in the plasma and follicular fluid of animals and humans. In an earlier study, we showed that increased oleic acid (OA) concentrations affected the function of cultured bovine granulosa cells (GCs). Here, we focus on genome wide effects of increased OA concentrations. Results Our data showed that 413 genes were affected, of which 197 were down- and 216 up-regulated. Specifically, the expression of FSH-regulated functional key genes, CCND2, LHCGR, INHA and CYP19A1 and 17-β-estradiol (E2) production were reduced by OA treatment, whereas the expression of the fatty acid transporter CD36 was increased and the morphology of the cells was changed due to lipid droplet accumulation. Bioinformatic analysis revealed that associated pathways of the putative upstream regulators “FSH” and “Cg (choriogonadotropin)” were inhibited and activated, respectively. Down-regulated genes are over-represented in GO terms “reproductive structure/system development”, “ovulation cycle process”, and “(positive) regulation of gonadotropin secretion”, whereas up-regulated genes are involved in “circulatory system development”, “vasculature development”, “angiogenesis” or “extracellular matrix/structure organization”. Conclusions From these data we conclude that besides inhibiting GC functionality, increased OA levels seemingly promote angiogenesis and tissue remodelling, thus suggestively initiating a premature fulliculo-luteal transition. In vivo this may lead to impeded folliculogenesis and ovulation, and cause sub-fertility.

Sign in / Sign up

Export Citation Format

Share Document