scholarly journals “All-In-One” Genetic Tool Assessing Endometrial Receptivity for Personalized Screening of Female Sex Steroid Hormones

2021 ◽  
Vol 9 ◽  
Author(s):  
Pavel Deryabin ◽  
Alisa Domnina ◽  
Inga Gorelova ◽  
Maxim Rulev ◽  
Mariya Petrosyan ◽  
...  
Keyword(s):  
Steroid Hormones ◽  
Luteal Phase ◽  
Embryo Implantation ◽  
Human Mesenchymal Stem Cells ◽  
Endometrial Receptivity ◽  
Patient Specific ◽  
Human Diploid Fibroblasts ◽  
Genetic Tool ◽  
Personalized Approach

Endometrium is the uterine lining that undergoes hundreds of cycles of proliferation, differentiation, and desquamation throughout a woman's reproductive life. Recently, much attention is paid to the appropriate endometrial functioning, as decreased endometrial receptivity is stated to be one of the concerns heavily influencing successes of embryo implantation rates and the efficacy of in vitro fertilization (IVF) treatment. In order to acquire and maintain the desired endometrial receptivity during IVF cycles, luteal phase support by various progestagens or other hormonal combinations is generally recommended. However, today, the selection of the specific hormonal therapy during IVF seems to be empirical, mainly due to a lack of appropriate tools for personalized approach. Here, we designed the genetic tool for patient-specific optimization of hormonal supplementation schemes required for the maintenance of endometrial receptivity during luteal phase. We optimized and characterized in vitro endometrial stromal cell (ESC) decidualization model as the adequate physiological reflection of endometrial sensitivity to steroid hormones. Based on the whole transcriptome RNA sequencing and the corresponding bioinformatics, we proposed that activation of the decidual prolactin (PRL) promoter containing ancient transposons MER20 and MER39 may reflect functioning of the core decidual regulatory network. Furthermore, we cloned the sequence of decidual PRL promoter containing MER20 and part of MER39 into the expression vector to estimate the effectiveness of ESC decidual response and verified sensitivity of the designed system. We additionally confirmed specificity of the generated tool using human diploid fibroblasts and adipose-derived human mesenchymal stem cells. Finally, we demonstrated the possibility to apply our tool for personalized hormone screening by comparing the effects of natural progesterone and three synthetic analogs (medroxyprogesterone 17-acetate, 17α-hydroxyprogesterone caproate, dydrogesterone) on decidualization of six ESC lines obtained from patients planning to undergo the IVF procedure. To sum up, we developed the “all-in-one” genetic tool based on the MER20/MER39 expression cassette that provides the ability to predict the most appropriate hormonal cocktail for endometrial receptivity maintenance specifically and safely for the patient, and thus to define the personal treatment strategy prior to the IVF procedure.

scholarly journals Bu Shen Zhu Yun Decoction Improves Endometrial Receptivity via VEGFR-2-Mediated Angiogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Li Li ◽  
Huabo Jiang ◽  
Xuecong Wei ◽  
Dandan Geng ◽  
Ming He ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Embryo Implantation ◽  
Mapk Signaling ◽  
Endometrial Receptivity ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
Nuclear Antigen ◽  
Vitro Fertilization

Vascular endothelial growth factor receptor-2 (VEGFR-2) regulates the mitogen-activated protein kinase (MAPK) signaling pathway and plays an important role in angiogenesis. Bu Shen Zhu Yun decoction (BSZYD) can improve endometrial receptivity and embryo implantation rates in patients undergoing in vitro fertilization. However, whether BSZYD improves endometrial receptivity via angiogenesis remains unclear. Here, we investigated the effects of BSZYD on the proliferation, migration, and angiogenesis of human endometrial microvascular endothelial cells (HEMECs) and found that BSZYD upregulated the expression of cyclin D1, matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen (PCNA) in HEMECs. Cell Counting Kit 8 assay, scratch-wound assay, and Tube Formation Assay results showed that BSZYD promoted the proliferation, migration, and angiogenesis of HEMECs. Western blot analysis results revealed the activation of the MAPK signaling pathway by BSZYD through the upregulation of VEGF and VEGFR-2 expression. Together, these findings highlight the novel mechanism underlying BSZYD-mediated improvement in endometrial receptivity through the MAPK signaling pathway.

Human chorionic gonadotropin improves endometrial receptivity by increasing the expression of homeobox A10

2020 ◽  
Vol 26 (6) ◽  
pp. 413-424
Author(s):  
Mengchen Zhu ◽  
Shanling Yi ◽  
Xiaomin Huang ◽  
Junan Meng ◽  
Haixiang Sun ◽  
...  
Keyword(s):  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Endometrial Stromal Cells ◽  
Healthy Control ◽  
Hcg Receptor ◽  
Methyltransferase 1

Abstract Homeobox A10 (HOXA10) is a characterized marker of endometrial receptivity. The mechanism by which hCG intrauterine infusion promotes embryo implantation is still unclear. This study seeks to investigate whether hCG improves endometrial receptivity by increasing expression of HOXA10. HOXA10 expression with human chorionic gonadotropin stimulation was analyzed in vitro and in vivo. Our results demonstrate that HOXA10 was decreased in the endometria of recurrent implantation failure patients compared to that in the healthy control fertile group, also we observed that hCG intrauterine infusion increased endometrial HOXA10 expression. HOXA10, blastocyst-like spheroid expansion area was increased, whereas DNA (cytosine-5-)-methyltransferase 1 was decreased when human endometrial stromal cells (hESCs) were treated with 0.2 IU/ml of hCG for 48 h. HOXA10 promoter methylation was also reduced after hCG treatment. Collagen XV (ColXV) can repress the expression of DNA (cytosine-5-)-methyltransferase 1, and hCG treatment increased the expression of ColXV. However, when the hESCs were treated with LH/hCG receptor small interfering RNA to knock down LH/hCG receptor, hCG treatment failed to repress DNA (cytosine-5-)-methyltransferase 1 expression or to increase ColXV expression. Our findings suggest that hCG may promote embryo implantation by increasing the expression of HOXA10.

scholarly journals Value of endometrial echo pattern transformation after hCG trigger in predicting IVF pregnancy outcome: a prospective cohort study

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Zhaojuan Hou ◽  
Qiong Zhang ◽  
Jing Zhao ◽  
Aizhuang Xu ◽  
Aihua He ◽  
...  
Keyword(s):  
Cohort Study ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Embryo Implantation ◽  
Implantation Rate ◽  
Endometrial Receptivity ◽  
Roc Curve Analysis ◽  
Vitro Fertilization ◽  
Hcg Trigger

Abstract Background There is much value in identifying non-invasive ways of measuring endometrial receptivity, as it has the potential to improve outcomes following in vitro fertilization (IVF). It has been suggested that endometrial echogenicity on the day of hCG administration was a good marker of endometrial receptivity. In the daily practice, we notice that patients with non-homogeneous hyperechoic endometrium on the embryo transfer day usually have lower pregnancy rates. We therefore extended the research onward transformation of echo pattern after hCG trigger to analyze the relationship between endometrial echogenicity transformation and IVF outcomes. Methods A total of 146 infertile women undergoing their first IVF cycle were recruited in the prospective cohort study from August 2017 through August 2018. A series of endometrial echo pattern monitoring was carried out in these patients after hCG trigger: hCG day, from 1 through 3 days after ovum pick-up (OPU + 1, OPU + 2, OPU + 3). Results The endometrial echogenicity value was calculated as the ratio of the hyperechogenic endometrial area over the whole endometrial area. Clinical pregnancy rate and embryo implantation rate had positive relationship with echogenicity value. The ROC curve analysis of endometrial echogenicity showed the area under curve was greatest on the second day after oocyte retrieval (OPU + 1, 2, 3 were 0.738, 0.765, 0.714 respectively) versus pregnancy. Endometrial echogenicity value on OPU + 2 had a higher predictive efficiency, and the cutoff value was 76.5%. The sensitivity was 61.3% and specificity was 82.0%. When putting the cut-off at <60%, the sensitivity was 93.8% and the specificity was 23.1%. Conclusions The endometrial echogenicity value on OPU + 2 was recommended to evaluate endometrial receptivity. It seemed appropriate for clinicians to provide a ‘freeze all’ IVF cycle and transfer in a subsequent frozen-thawed embryos cycle when echogenicity value <60% on OPU + 2. Trial registration The registration number was ChiCTR-OOC-17012214 and the registration date was August 1st, 2017.

scholarly journals CXCL12 enhances pregnancy outcome via improvement of endometrial receptivity in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hwa Seon Koo ◽  
Min-Ji Yoon ◽  
Seon-Hwa Hong ◽  
Jungho Ahn ◽  
Hwijae Cha ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Therapeutic Strategy ◽  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Successful Pregnancy ◽  
Vessel Formation ◽  
Evidence Based Treatments ◽  
Chemokine Cxcl12 ◽  
Cd34 Expression

AbstractSuccessful pregnancy inevitably depends on the implantation of a competent embryo into a receptive endometrium. Although many substances have been suggested to improve the rate of embryo implantation targeting enhancement of endometrial receptivity, currently there rarely are effective evidence-based treatments to prevent or cure this condition. Here we strongly suggest minimally-invasive intra-uterine administration of embryo-secreted chemokine CXCL12 as an effective therapeutic intervention. Chemokine CXCL12 derived from pre- and peri-implanting embryos significantly enhances the rates of embryo attachment and promoted endothelial vessel formation and sprouting in vitro. Consistently, intra-uterine CXCL12 administration in C57BL/6 mice improved endometrial receptivity showing increased integrin β3 and its ligand osteopontin, and induced endometrial angiogenesis displaying increased numbers of vessel formation near the lining of endometrial epithelial layer with higher CD31 and CD34 expression. Furthermore, intra-uterine CXCL12 application dramatically promoted the rates of embryo implantation with no morphologically retarded embryos. Thus, our present study provides a novel evidence that improved uterine endometrial receptivity and enhanced angiogenesis induced by embryo-derived chemokine CXCL12 may aid to develop a minimally-invasive therapeutic strategy for clinical treatment or supplement for the patients with repeated implantation failure with less risk.

scholarly journals Regulation of homeobox A10 expression in the primate endometrium by progesterone and embryonic stimuli

Reproduction ◽  
2007 ◽  
Vol 134 (3) ◽  
pp. 513-523 ◽  
Author(s):  
G B Godbole ◽  
D N Modi ◽  
C P Puri
Keyword(s):  
Growth Factor ◽  
Luteal Phase ◽  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Macaca Radiata ◽  
Endometrial Cells ◽  
Preimplantation Stage ◽  
Bonnet Monkey ◽  
Embryonic Signaling

Homeobox A10 (HOXA10), a member of abdominal B subclass of homeobox genes, is responsible for uterine homeosis during development. Intriguingly, in the adult murine uterus, HOXA10 has been demonstrated to play important roles in receptivity, embryo implantation, and decidualization. However, the roles of HOXA10 in the primate endometrium are not known. To gain insights into the roles of HOXA10 in the primate endometrium, its expression was studied in the endometria of bonnet monkey (Macaca radiata) in the receptive phase and also in the endometria of monkeys treated with antiprogestin onapristone (ZK98.299) or in conception cycle where the presence of preimplantation stage blastocyst was verified. In addition, the mRNA expression of HOXA11 and insulin-like growth factor-binding protein 1 (IGFBP1) was evaluated by real-time PCR in these animals.The results revealed that HOXA10 in the luteal phase primate endometrium is differentially expressed in the functionalis and the basalis zones, which is modulated in vivo by progesterone and also by the signals from the incoming embryo suggesting the involvement of HOXA10 in the process of establishment of pregnancy in primates. In addition, the results also demonstrated that the expression of IGFBP1 but not HOXA11 is coregulated with HOXA10 in the endometria of these animals. The pattern of changes in the expression of HOXA10 in response to the two stimuli suggests that endometrial receptivity and implantation not only requires a synchrony of maternal and embryonic signaling on endometrial cells in the primates but there also exists a controlled differential response among the cells of various uterine compartments.

Hemodynamic study of arteriovenous fistulas for hemodialysis access

Vascular ◽  
2012 ◽  
Vol 21 (1) ◽  
pp. 54-62 ◽  
Author(s):  
Ankur Chandra ◽  
Doran Mix ◽  
Nicole Varble
Keyword(s):  
Surgical Planning ◽  
Fluid Dynamic ◽  
Patient Specific ◽  
Dialysis Access ◽  
Arteriovenous Fistulas ◽  
Personalized Approach ◽  
Future Work ◽  
Hemodynamic Study

Dialysis access failure and associated complications represent a major cause of morbidity in patients with renal failure. This is due to an incomplete understanding of the hemodynamics associated with both arteriovenous fistula (AVF) successes and complications. Several decades of research have been performed studying these complex hemodynamic changes. This review provides an overview of work undertaken in three key areas of AVF hemodynamic research: mathematical modeling, in vivo fluid dynamic measurements and in vitro fluid dynamic modeling. Current and future work is then summarized involving the application of a comprehensive, systematic study of dialysis access hemodynamics. The ultimate goal is the ability to predict clinical outcomes of dialysis access procedures through personalized, patient-specific surgical planning. If successful, this type of tool would allow surgeons to predict multiple-dialysis access intervention outcomes and choose a personalized approach to maximize success.

scholarly journals Administration of a herbal formulation enhanced blastocyst implantation via IκB activation in mouse endometrium

2020 ◽  
Author(s):  
Songhee Jeon ◽  
Quan Feng Liu ◽  
Hua Cai ◽  
Ha Jin Jeong ◽  
Su-Hyun Kim ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
Water Extract ◽  
Treated Group ◽  
Endometrial Receptivity ◽  
Implantation Failure ◽  
Herbal Formulation ◽  
Blastocyst Implantation ◽  
Implantation Sites

Abstract Background: BaelanChagsangBang (BCB), a herbal formulation consisting of eleven herbs, may be prescribed as a reproductive functional supplement to improve ovulation and implantation during the treatment of infertility and recurrent abortion in Korean Medicine. This study aimed to investigate the effects and action mechanisms of water-extracted BCB on endometrial receptivity and blastocyst implantation under normal conditions and in a mifepristone (RU486)-induced implantation failure murine model.Methods: In vitro, the antioxidant potentials of BCB were evaluated using DPPH and superoxide anion radical scavenging assays and a DCFH-DA assay, and the cytotoxic and cytoprotective effects of BCB were confirmed using an MTT assay. In vivo, C57BL/6 female mice (n = 6 per group) orally received BCB (300 mg/kg/day), a dose similar to that used clinically, from 7 days before pregnancy until the end of the experiment. On day 4 of pregnancy, RU486 (4 mg/kg) was injected subcutaneously to induce implantation failure. The effect of BCB on embryo implantation was evaluated by implantation rate analysis, histological examination, and western blotting of uterus tissues.Results: BCB water extract showed strong anti-oxidative and cytoprotective effects in vitro. In vivo administration of BCB water extract increased the number of newborn pups in BCB-treated mice versus sham-treated mice under normal conditions and improved the number of implantation sites in pregnant mice despite RU486 injection. BCB increased the protein levels of cyclooxygenase-2 and inducible nitric oxide synthase through IκB activation. Moreover, the expression levels of matrix metalloproteinases (MMPs) at uterus implantation sites were up-regulated in the BCB-treated group as compared with those in the RU486-treated group. Conclusion: These results show BCB improved embryo implantation through IκB activation in our mouse model and suggest that BCB has therapeutic potential in the context of poor endometrial receptivity.

scholarly journals Embryo-Derived Chemokine CXCL12 Enhances Pregnancy Outcome via Improvement of Endometrial Receptivity

2020 ◽  
Author(s):  
Hwa Seon Koo ◽  
Min-Ji Yoon ◽  
Seon-Hwa Hong ◽  
Jungho Ahn ◽  
Hwijae Cha ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
Research Work ◽  
Endometrial Receptivity ◽  
Invasive Treatment ◽  
Vessel Formation ◽  
Non Invasive ◽  
Evidence Based Treatments ◽  
Chemokine Cxcl12

Abstract Background: Successful pregnancy inevitably depends on the implantation of a competent embryo into a receptive endometrium. Although a remarkable improvement of assisted reproductive technology (ART) has been achieved over the last few decades, there are still a number of infertile women experiencing frequent ART failure after repeated attempts due to many unsolved problems including repeated failure of implantation. Many substances have been suggested to improve the rates of embryo implantation by enhancing the endometrial receptivity for the patients who are suffering from repeated failure of implantation. However, despite these numerous extensive research work, there are currently no effective evidence-based treatments to prevent or cure this condition. Therefore, here we aim to suggest non-invasive intra-uterine administration of embryo-secreted chemokine CXCL12 as an effective therapeutic intervention to solve this problem.Results: We demonstrated that chemokine CXCL12 is derived from pre- and peri-implanting embryos and its interaction with endometrial CXCR4 and CXCR7 enhances endometrial receptivity and significantly promoted endothelial vessel formation and sprouting in vitro. Consistently, intra-uterine CXCL12 administration in vivo, which is a completely non-invasive treatment strategy, improved endometrial receptivity showing increased integrin b3 and its ligand osteopontin, and induced endometrial angiogenesis displaying increased numbers of vessel formation near the lining of endometrial epithelial layer with higher CD31 and CD34 expression. Furthermore, intra-uterine CXCL12 application dramatically promoted the rates of embryo implantation with no morphologically retarded embryos. Conclusions: Our present study provides a novel evidence that improved uterine endometrial receptivity and enhanced angiogenesis induced by embryo-derived chemokine CXCL12 may aid to develop a non-invasive therapeutic strategy for clinical treatment or supplement for the patients with repeated implantation failure with less risk.

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