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      Electroacupuncture Improves Pregnancy Outcomes in Rats with Thin Endometrium by Promoting the Expression of Pinopode-Related Molecules

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          Abstract

          A thin endometrium affects the success of assisted reproduction due to low endometrial receptivity. Acupuncture improves endometrial receptivity and promotes the formation of pinopodes, the ultrastructure marker implantation window. However, the specific underlying mechanisms remain unclear. In this study, the efficacy of acupuncture treatment and its underlying mechanism were investigated by analyzing pregnancy rate, pinopode formation, and related molecular markers in thin endometrium model rats. Absolute ethanol (95%) was injected into the uteruses of female Sprague-Dawley rats to construct a thin endometrium model. In this model, acupuncture stimulation at EX-CA1, SP6, and CV4 ameliorated the pregnancy rate. Significantly increased embryo implantation, endometrial thickness, numbers of glands, and blood vessels were observed in the electroacupuncture (EA) group compared to the model group. The number of pinopodes in the EA group was abundant, with a shape similar to that of the control group. Additionally, significantly higher expression levels of pinopode-related markers, including integrin αv β3, homeobox A10 (HOXA10), heparin-binding EGF-like growth factor (HBEGF), estrogen receptor alpha (ER α), and progesterone receptor (PR), were observed in the EA group than those in the model group. In conclusion, EA had a positive effect on the endometrial receptivity of thin endometrium model rats by improving pinopode formation through multiple molecular targets.

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          Most cited references71

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          Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.

          Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been recently implicated to have a functional role in a number of other reproductive events. The physiological effects of progesterone are mediated by the progesterone receptor (PR), a member of the nuclear receptor superfamily of transcription factors. In most cases the PR is induced by estrogen, implying that many of the in vivo effects attributed to progesterone could also be the result of concomitantly administered estrogen. Therefore, to clearly define those physiological events that are specifically attributable to progesterone in vivo, we have generated a mouse model carrying a null mutation of the PR gene using embryonic stem cell/gene targeting techniques. Male and female embryos homozygous for the PR mutation developed normally to adulthood. However, the adult female PR mutant displayed significant defects in all reproductive tissues. These included an inability to ovulate, uterine hyperplasia and inflammation, severely limited mammary gland development, and an inability to exhibit sexual behavior. Collectively, these results provide direct support for progesterone's role as a pleiotropic coordinator of diverse reproductive events that together ensure species survival.
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            Integrin Signaling

            Cells reside in a protein network, the extracellular matrix (ECM), which they secrete and mold into the intercellular space. The ECM exerts profound control over cells. The effects of the matrix are primarily mediated by integrins, a family of cell surface receptors that attach cells to the matrix and mediate mechanical and chemical signals from it. These signals regulate the activities of cytoplasmic kinases, growth factor receptors, and ion channels and control the organization of the intracellular actin cytoskeleton. Many integrin signals converge on cell cycle regulation, directing cells to live or die, to proliferate, or to exit the cell cycle and differentiate.
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              Endometrial thickness and pregnancy rates after IVF: a systematic review and meta-analysis.

              Thin endometrium on ultrasound in the course of ovarian hyperstimulation has been thought to be associated with poor success rates after IVF, even in the absence of prior intrauterine surgery or infection. To assess the clinical significance of endometrial thickness (EMT) for IVF outcome, we performed a systematic review and meta-analysis. The electronic databases Pubmed, Cochrane and Embase were searched up to October 2013 for articles that studied the association between EMT and IVF outcome. The articles had to be written in the English or Dutch language. Studies were included if two-by-two tables for EMT and pregnancy rates could be constructed. Study quality was scored using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Summary receiver operating characteristic (sROC) curves were estimated to assess the accuracy of EMT in the prediction of pregnancy. In addition, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a Mantel-Haenszel random effect model expressing the association between EMT and pregnancy chances. Meta-regression was performed to determine if female age and number of oocytes at retrieval interacted in the estimated effect of EMT on IVF outcome. A total of 1170 studies was retrieved by the search. The overall quality of the 22 studies included in the review and meta-analysis was moderate. The estimated sROC curve indicated a virtually absent discriminatory capacity of EMT in the prediction of pregnancy. A thin endometrium (≤ 7 mm) was observed in only 2.4% of the reported cases (260/10 724). In these cases a trend towards lower ongoing pregnancy and live birth rates for women with EMT ≤ 7 mm was observed [OR 0.38 (95% CI 0.09-1.5)]. The probability of clinical pregnancy for an EMT ≤ 7 mm was significantly lower compared with cases with EMT > 7 mm [23.3% versus 48.1%, OR 0.42 (95% CI 0.27-0.67)]. Positive and negative predictive values for the outcome of clinical pregnancy 77 and 48%, respectively. The relationship between the number of oocytes and female age on the one hand and pregnancy on the other hand was very weak making correction for these variables unfeasible. Current data indicate that EMT has a limited capacity to identify women who have a low chance to conceive after IVF. The frequently reported cut-off of 7 mm is related to a lower chance of pregnancy, but occurs infrequently. The use of EMT as a tool to decide on cycle cancellation, freezing of all embryos or refraining from further IVF treatment seems not to be justified based on the current meta-analysis. Further research is needed to investigate the real independent significance of EMT in IVF. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2021
                15 April 2021
                : 2021
                : 6658321
                Affiliations
                1Acupuncture and Tuina College, Nanjing University of Traditional Chinese Medicine, Nanjing 210023, China
                2Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Traditional Chinese Medicine, Nanjing 210023, China
                3Xuzhou Medical University, Xuzhou 221004, China
                Author notes

                Academic Editor: Renato T Souza

                Author information
                https://orcid.org/0000-0002-2533-9321
                https://orcid.org/0000-0002-7568-8669
                https://orcid.org/0000-0001-6781-7750
                https://orcid.org/0000-0002-0268-590X
                https://orcid.org/0000-0001-9435-3699
                https://orcid.org/0000-0002-6594-8260
                https://orcid.org/0000-0002-8814-6180
                https://orcid.org/0000-0003-0680-3333
                https://orcid.org/0000-0002-0408-2045
                https://orcid.org/0000-0003-4006-3009
                Article
                10.1155/2021/6658321
                8062184
                33937407
                c1cabb88-7f3c-4cd7-9a66-2bfe0bee2041
                Copyright © 2021 Jin Xi et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 December 2020
                : 27 March 2021
                : 3 April 2021
                Funding
                Funded by: Graduate Research and Innovation Projects of Jiangsu Province
                Award ID: SJKY19_1439
                Funded by: National Natural Science Foundation of China
                Award ID: 81804179
                Award ID: 81873371
                Categories
                Research Article

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