PMID- 34216338 OWN - NLM STAT- MEDLINE DCOM- 20220118 LR - 20220118 IS - 1573-4978 (Electronic) IS - 0301-4851 (Linking) VI - 48 IP - 6 DP - 2021 Jun TI - Endometrial gene expression profiling of recurrent implantation failure after in vitro fertilization. PG - 5075-5082 LID - 10.1007/s11033-021-06502-x [doi] AB - Recurrent implantation failure (RIF) is diagnosed when good-quality embryos repeatedly fail to implant after transfer in several in vitro fertilization (IVF) treatment cycles. Different expression profiles in maternal mRNAs could be referring to many diseases including RIF. This study aimed to reveal significantly dysregulated selected genes expression between healthy fertile women and RIF patients in the implantation window days of the natural menstrual cycle. MME, WWC1, TNC, and FOXP3 genes were chosen as target genes regarding their possible relations with the implantation process. Pathways with these genes were identified and the relationship between these pathways and RIF was investigated. In this study, the endometrial biopsy samples were collected in the secretory phase (cycle day 20-24) of the menstrual cycle from RIF patients (n = 34) and healthy fertile controls (n = 34). After "Pathway and network-oriented GWAS analysis" (PANOGA) and "Kyoto Encyclopedia of Genes and Genomes" (KEGG) pathway analysis; "Membrane Metalloendopeptidase" (MME), "WW and C2 Domain Containing 1" (WWC1), "Tenascin C" (TNC) and "Forkhead Box P3" (FOXP3) genes were chosen as target genes by regarding their possible relation with implantation process. Detection of differences in mRNA expressions between the control group and RIF patients has been performed with the droplet digital PCR (ddPCR) method. Results of the study showed that MME and WWC1 genes expression levels are significantly (p < 0,05) up-regulated 4.9 and 5.2 times respectively and TNC gene expression level is significantly (p < 0,05) down-regulated 9 times in the RIF samples compared to the control group. However, no statistically significant difference was observed between the patient group and the control group in the expression of the FOXP3 gene (p < 0.05). Changes are observed in the expression of the renin-angiotensin system pathway in which the MME gene is involved in the implantation process. The increase in MME gene expression can be speculated to cause implantation failure by restricting the invasion of trophoblast cells. Increasing WWC1 gene expression in the Hippo signaling pathway inhibits "Yes-associated protein 1" (YAP) expression, which is a transcriptional cofactor. Inhibition of YAP protein expression may impair the implantation process by causing the failure of endometrial decidualization. The TNC gene is located in the focal adhesion pathway and this pathway reduces cell adhesion on the endometrial surface to facilitate the attachment of the embryo to the endometrium. The reason for implantation failure might be that the intercellular connections are not suitable for implantation as a result of decreased expression of the focal adhesion pathway in which the TNC gene is effective. Considering the relations between the pathways of the target genes and the implantation process, changes in the expression of target genes might be a cause of RIF. CI - (c) 2021. The Author(s), under exclusive licence to Springer Nature B.V. FAU - Albayrak, Irem Gulfem AU - Albayrak IG AD - Molecular Biology and Genetics Department, Faculty of Science, Istanbul University, 34134, Istanbul, Fatih, Turkey. AD - Molecular Biology and Genetics Department, Faculty of Engineering and Natural Sciences, Uskudar University, 34662, Istanbul, Uskudar, Turkey. FAU - Azhari, Fatemeh AU - Azhari F AD - Department of Molecular Medicine, Faculty of Medicine, Istanbul University, 34093, Istanbul, Capa, Turkey. FAU - Colak, Ezgi Nur AU - Colak EN AD - Molecular Biology and Genetics Department, Faculty of Science, Istanbul University, 34134, Istanbul, Fatih, Turkey. FAU - Balci, Burcin Karamustafaoglu AU - Balci BK AD - Department of Obstetrics and Gynaecology, Faculty of Medicine, Istanbul University, 34093, Istanbul, Capa, Turkey. FAU - Ulgen, Ege AU - Ulgen E AD - Department of Biostatistics and Medical Informatics, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Atasehir, Turkey. FAU - Sezerman, Ugur AU - Sezerman U AD - Department of Biostatistics and Medical Informatics, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Atasehir, Turkey. FAU - Bastu, Ercan AU - Bastu E AD - Department of Obstetrics and Gynaecology, Acibadem Fulya Hospital, 34349, Istanbul, Besiktas, Turkey. FAU - Gunel, Tuba AU - Gunel T AUID- ORCID: 0000-0003-3514-5210 AD - Molecular Biology and Genetics Department, Faculty of Science, Istanbul University, 34134, Istanbul, Fatih, Turkey. gunel@istanbul.edu.tr. LA - eng GR - 32431/Bilimsel Arastirma Projeleri Birimi, Istanbul Universitesi/ PT - Journal Article DEP - 20210703 PL - Netherlands TA - Mol Biol Rep JT - Molecular biology reports JID - 0403234 RN - 0 (FOXP3 protein, human) RN - 0 (Forkhead Transcription Factors) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (TNC protein, human) RN - 0 (Tenascin) RN - 0 (WWC1 protein, human) RN - 0 (YAP-Signaling Proteins) RN - 0 (YAP1 protein, human) RN - EC 3.4.24.11 (Neprilysin) SB - IM MH - Adult MH - Embryo Implantation/*genetics/physiology MH - Endometrium/*metabolism MH - Female MH - Fertilization in Vitro/*methods MH - Forkhead Transcription Factors/genetics MH - Gene Expression/genetics MH - Gene Expression Profiling/methods MH - Hippo Signaling Pathway/genetics MH - Humans MH - Intracellular Signaling Peptides and Proteins/genetics MH - Microarray Analysis MH - Neprilysin/genetics MH - Tenascin/genetics MH - Transcriptome/genetics MH - Turkey MH - YAP-Signaling Proteins/genetics OTO - NOTNLM OT - Endometrium OT - Gene Expression OT - IVF OT - RIF OT - mRNA EDAT- 2021/07/04 06:00 MHDA- 2022/01/19 06:00 CRDT- 2021/07/03 12:11 PHST- 2020/12/17 00:00 [received] PHST- 2021/06/17 00:00 [accepted] PHST- 2021/07/04 06:00 [pubmed] PHST- 2022/01/19 06:00 [medline] PHST- 2021/07/03 12:11 [entrez] AID - 10.1007/s11033-021-06502-x [pii] AID - 10.1007/s11033-021-06502-x [doi] PST - ppublish SO - Mol Biol Rep. 2021 Jun;48(6):5075-5082. doi: 10.1007/s11033-021-06502-x. Epub 2021 Jul 3.