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Alterations in complement and coagulation pathways of human placentae subjected to in vitro fertilization and embryo transfer in the first trimester.

ABSTRACT: The mechanisms underlying the potential risks of in vitro fertilization and embryo transfer (IVF-ET) have not been fully elucidated. The aim of this study was to explore changes in the complement and coagulation pathways in placentae subjected to IVF-ET in the first trimester compared to placentae from normal pregnancies. Four placenta samples in the first trimester were obtained from patients undergoing IVF-ET owing to oviductal factors only. An additional 4 control placentae were obtained from volunteers with normal pregnancies. A GeneChip Affymetrix HG-U133 Plus 2.0 Array was utilized to analyze the changes in gene expression between the normal and IVF-ET placentae. Differentially expressed genes (DEGs) were analyzed using the Database for Annotation and Visualization and Integrated Discovery bioinformatics resource, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Using real-time PCR, we confirmed the obtained microarray data in 10 dysregulated genes. Five of the gene products were further analyzed by immunohistochemistry (IHC) to determine their protein expression and localization. A total of fifty DEGs were identified in the complement and coagulation pathways in the IVF-ET treated placentae: 38 upregulated and 12 down-regulated. KEGG pathway analysis indicated that IVF-ET manipulation substantially over-activated the coagulation and complement pathways, while urokinase plasminogen activator- and urokinase plasminogen activator receptor-mediated trophoblastic invasion and tissue remodeling were inhibited. Furthermore, the 5 proteins analyzed by IHC were found to be localized specifically to the placenta. This is the first study to compare DEGs relating to the placental complement and coagulation pathways from patients undergoing IVF-ET treatment compared to those undergoing normal pregnancy. These findings identified valuable biomarkers and potential novel therapeutic targets to combat the unfavorable effects of IVF-ET.

SUBMITTER: Zhao L

PROVIDER: S-EPMC6946305 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Alterations in complement and coagulation pathways of human placentae subjected to in vitro fertilization and embryo transfer in the first trimester.

Zhao Liang L Sun Lifang L Zheng Xiuli X Liu Jingfang J Zheng Rong R Yang Rui R Wang Ying Y

Medicine 20191101 44

The mechanisms underlying the potential risks of in vitro fertilization and embryo transfer (IVF-ET) have not been fully elucidated. The aim of this study was to explore changes in the complement and coagulation pathways in placentae subjected to IVF-ET in the first trimester compared to placentae from normal pregnancies. Four placenta samples in the first trimester were obtained from patients undergoing IVF-ET owing to oviductal factors only. An additional 4 control placentae were obtained from ...[more]

PMID: 31689742

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Project description:BackgroundThe placenta is a highly specialized temporary organ that is related to fetal development and pregnancy outcomes, and epidemiological data demonstrate an increased risk of placental abnormality after in vitro fertilization and embryo transfer (IVF-ET).MethodsThis study examines alterations in the transcriptome profile of first-trimester placentas from IVF-ET pregnancies and analyzes the potential mechanisms that play a role in the adverse perinatal outcomes associated with IVF-ET procedures. Four human placental villi from first-trimester samples were obtained through fetal bud aspiration from patients subjected to IVF-ET due to oviductal factors. An additional four control human placental villi were derived from a group of subjects who spontaneously conceived a twin pregnancy. We analyzed their transcriptomes by microarray. Then, RT-qPCR and immunohistochemistry were utilized to analyze several dysregulated genes to validate the microarray results. Biological functions and pathways were analyzed with bioinformatics tools.ResultsA total of 3405 differentially regulated genes were identified as significantly dysregulated (> 2-fold change; P < 0.05) in the IVF-ET placenta in the first trimester: 1910 upregulated and 1495 downregulated genes. Functional enrichment analysis of the differentially regulated genes demonstrated that the genes were involved in more than 50 biological processes and pathways that have been shown to play important roles in the first trimester in vivo. These pathways can be clustered into coagulation cascades, immune response, transmembrane signaling, metabolism, cell cycle, stress control, invasion and vascularization. Nearly the same number of up- and downregulated genes participate in the same biological processes related to placental development and maintenance. Procedures utilized in IVF-ET altered the expression of first-trimester placental genes that are critical to these biological processes and triggered a compensatory mechanism during early implantation in vivo.ConclusionThese data provide a potential basis for further analysis of the higher frequency of adverse perinatal outcomes following IVF-ET, with the ultimate goal of developing safer IVF-ET protocols.

Project description:IntroductionThe infertile patient's knowledge, attitude, and practice (KAP) toward embryo transfer may affect treatment outcomes and the mental health of women who underwent in vitro fertilization-embryo transfer (IVF-ET). This study aimed to investigate the KAP of embryo transfer among women who underwent IVF-ET.MethodsThis cross-sectional study was conducted on women who underwent IVF-ET at our Hospital between May 2023 and November 2023, using a self-designed questionnaire.ResultsA total of 614 valid questionnaires were finally included. The mean KAP scores were 19.46 ± 5.06 (possible range: 0 28), 39.41 ± 5.20 (possible range: 12-60), and 48.02 ± 6.75 (possible range: 0-60), respectively. The structural equation model demonstrated that knowledge has a direct effect on attitude (β = 0.27, p < 0.001) and attitude has a direct effect on practice (β = 0.55, p < 0.001) and anxiety (β = 0.59, p < 0.001). Moreover, multivariable linear regression analysis showed that anxiety score [coefficient = 0.09, 95% confidence interval (CI): 0.03-0.16, p = 0.003], BMI (coefficient = 0.09, 95%CI: 0.03-0.16, p = 0.003), education (coefficient = 5.65-6.17, 95%CI: 1.09-10.7, p < 0.05), monthly per capita income (coefficient = 1.20-1.96, 95% CI: 0.21-3.07, p = 0.05), reasons for IVF (coefficient = -1.33-1.19, 95% CI: -2.49-0.09, p < 0.05), and more than 5 years of infertility (coefficient = -1.12, 95% CI: -2.11-0.13, p = 0.026) were independently associated with sufficient knowledge. Knowledge (coefficient = 0.19, 95% CI: 0.12-0.26, p < 0.001), anxiety (coefficient = 0.39, 95% CI: 0.34-0.45, p < 0.001), monthly per capita household income >10,000 (coefficient = 1.52, 95% CI: 0.61-2.43, p < 0.001), and three or more cycles of embryo transfer (coefficient = -2.69, 95% CI: -3.94-1.43, p < 0.001) were independently associated with active attitude. Furthermore, attitude (coefficient = 0.21, 95% CI: 0.11-0.30, p < 0.001) and anxiety (coefficient = 0.57, 95% CI: 0.49-0.65, p < 0.001) were independently associated with proactive practice.DiscussionWomen who underwent IVF-ET had inadequate knowledge and negative attitudes but proactive practice toward embryo transfer, which were affected by anxiety, income, and reasons for IVF. It is necessary to strengthen the continuous improvement of patient education to improve the management of embryo transfer.

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Alterations in complement and coagulation pathways of human placentae subjected to in vitro fertilization and embryo transfer in the first trimester.

Publications

Alterations in complement and coagulation pathways of human placentae subjected to in vitro fertilization and embryo transfer in the first trimester.

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