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 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.

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 Antiphospholipid Antibodies in Women Undergoing In Vitro Fertilization Treatment: Clinical Value of IgA Anti-β2glycoprotein I Antibodies Determination

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Odile Paulmyer-Lacroix ◽  
Laura Despierres ◽  
Blandine Courbiere ◽  
Nathalie Bardin
Keyword(s):  
In Vitro Fertilization ◽  
Antiphospholipid Antibodies ◽  
Therapeutic Strategy ◽  
Embryo Implantation ◽  
Anticardiolipin Antibodies ◽  
Clinical Value ◽  
Vitro Fertilization ◽  
Total Prevalence ◽  
Iga Antibodies

Implantation failure could be related to antiphospholipid antibodies (aPL). We retrospectively analyzed the usefulness of aPL determination in women undergoing IVF. Conventional aPL of the antiphospholipid syndrome, lupus anticoagulant (LA), anticardiolipin antibodies (aCL), anti-β2glycoprotein I (aβ2GPI) antibodies, and IgG and IgM isotypes as well as IgA isotype were analyzed in women presenting with at least two implantation failures after in vitro fertilization (IVF). In a population of 40 IVF patients, a total prevalence of 20% (8/40) of aPL was found, significantly different from that of the control population (100 healthy blood donors,P<0.0005). Among the panels of aPL tested, aβ2GPI IgA antibodies were the most prevalent (62.5% 5/8), significantly higher in IVF patients (12.5%, 5/40) than in controls (1%, 1/100) (P=0.01). No difference according to the numbers of IVF attempts and success of embryo implantation was found between aPL positive and negative IVF patients. In contrast, no accomplished pregnancy with full-term live birth was observed in aPL positive IVF patients. Altogether our data led us to propose aPL assessment, in particular aβ2GPI IgA antibodies, in support of IVF treated women. In a perspective way, an early aPL detection could be the basis for defining novel therapeutic strategy.

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 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 Granulocyte colony-stimulating factor as a checkpoint of the embryo invasive potential and endometrial receptivity

2019 ◽  
Vol 68 (1) ◽  
pp. 83-92
Author(s):  
Natalya I. Tapilskaya ◽  
Alexander M. Gzgzyan ◽  
Igor Yu. Kogan
Keyword(s):  
Embryo Implantation ◽  
Implantation Rate ◽  
Endometrial Receptivity ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Invasive Potential ◽  
Vitro Fertilization ◽  
Anti Inflammatory ◽  
Stimulating Factor

Granulocyte colony-stimulating factor (G-CSF) promotes proliferation, survival, and differentiation of myeloid-lineage cells, as well as normal hematopoietic cells. The immunomodulating effects of G-CSF, which consist in stimulating the Th2 biased type immune response, prevent the development of graft-versus-host disease (GvHD) and, as a special case of GvHD, are responsible for the embryo implantation into the endometrium after the embryo transfer. G-CSF stimulates subpopulations of neutrophils, which display anti-inflammatory properties and are involved in tissue regeneration. The increased secretion of annexin A1 and IL-10 ensures the anti-inflammatory and immunomodulating effects of neutrophils. This review article presents data from four meta-analyzes aimed to explore the efficiency of G-CSF on infertile women undergoing in vitro fertilization. These data demonstrate an increase in the embryo implantation rate and clinical pregnancy rate, which is provided by the change in the endometrial receptivity and/or the invasive potential of the developing embryo.

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

2020 ◽  
Vol 15 (1) ◽  
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 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 Enhancement of Endometrial Receptivity by Cnidium officinale through Expressing LIF and Integrins

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Tae-Wook Chung ◽  
Mi-Ju Park ◽  
Hoyoung Lee ◽  
Keuk-Jun Kim ◽  
Cheorl-Ho Kim ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Embryo Implantation ◽  
Implantation Rate ◽  
Endometrial Receptivity ◽  
Female Infertility ◽  
In Vivo Model ◽  
Cnidium Officinale ◽  
Ishikawa Cells

Improvement of endometrial receptivity is necessary for successful embryo implantation, and its impairment is associated with female infertility. In this study, we investigated the effect of the roots of Cnidium officinale Makino (CoM) on endometrial receptivity in both in vitro and in vivo model of embryo implantation. We found that CoM enhanced the adhesion of JAr cells to Ishikawa cells by stimulating expression of leukemia inhibitory factor (LIF) and integrins. In addition, blocking of LIFR using hLA or neutralization of integrins αV, β3, and β5 using antibodies significantly reduced the enhanced adhesion between JAr cell and CoM-treated Ishikawa cells, indicating that LIF and integrin play an important role in trophoblast-endometrium adhesion for embryo implantation. Furthermore, we identified that CoM significantly improved the implantation rate of blastocysts in the mouse model of RU-induced implantation failure. By collecting these results, here, we suggest that CoM has a therapeutic potential against female infertility associated with decreased endometrial receptivity.

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