PMID- 30216582 OWN - NLM STAT- MEDLINE DCOM- 20190923 LR - 20211204 IS - 1098-2795 (Electronic) IS - 1040-452X (Linking) VI - 85 IP - 10 DP - 2018 Oct TI - Upregulation of HB-EGF, Msx.1, and miRNA Let-7a by administration of calcitonin through mTOR and ERK1/2 pathways during a window of implantation in mice. PG - 790-801 LID - 10.1002/mrd.23061 [doi] AB - BACKGROUND: Successful implantation of embryos requires endometrial receptivity. Calcitonin is one of the factors influencing the implantation window. This study aimed to evaluate calcitonin effects on endometrial receptivity. To this end, the effects of calcitonin on the implantation window in the ovarian stimulation and the normal ovarian cycle were investigated by the morphological study of the endometrium as well as the expression of MSX.1, HB-EGF, and micro-RNA (miRNA) Let-7a; then the mechanisms of calcitonin effects were studied through the mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways. MATERIALS AND METHODS: A total of 64 Bulb/c mice were divided into two groups: Normal ovarian cycle and ovarian stimulation. Each group consisted of four subgroups: Ctrl, CT, PP242, and CT + PP242. Calcitonin and PP242 were injected on the fourth day of pregnancy and 24 hr later all the mice were killed. Uterine tissue samples were used for morphological analysis and the endometrial epithelial and the stromal cells were isolated from myometrium for evaluation of gene and protein expression. RESULTS: Ovarian stimulation increased the phosphorylation levels of mTOR and ERK1/2 and the expression of miRNA Let-7a. Calcitonin injection increased the expression of HB-EGF, Msx.1, and miRNA Let-7a in a normal ovarian cycle and in ovarian-stimulated mice. It also increased eukaryotic initiation factor 4E-binding protein 1 and ERK1/2 phosphorylation in normal ovarian cycles. CONCLUSION: Calcitonin improved the receptivity of the uterine endometrium by upregulation of the HB-EGF, Msx.1, and miRNA Let-7a likely through mTOR and ERK1/2 signaling pathway. CI - (c) 2018 Wiley Periodicals, Inc. FAU - Shokrzadeh, Naser AU - Shokrzadeh N AUID- ORCID: 0000-0002-8816-2797 AD - Immunology Research Center, Faculty Of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. FAU - Alivand, Mohammad Reza AU - Alivand MR AD - Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. FAU - Abedelahi, Ali AU - Abedelahi A AD - Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. FAU - Hessam Shariati, Mohammad Bakhtiar AU - Hessam Shariati MB AD - Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. FAU - Niknafs, Behrooz AU - Niknafs B AD - Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. LA - eng GR - 58330/Immunology Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran/International PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Reprod Dev JT - Molecular reproduction and development JID - 8903333 RN - 0 (Heparin-binding EGF-like Growth Factor) RN - 0 (MSX1 Transcription Factor) RN - 0 (MicroRNAs) RN - 0 (Msx1 protein, mouse) RN - 0 (mirnlet7 microRNA, mouse) RN - 9007-12-9 (Calcitonin) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.24 (Mapk1 protein, mouse) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) SB - IM MH - Animals MH - Calcitonin/*pharmacology MH - Embryo Implantation/*drug effects MH - Endometrium/*metabolism MH - Female MH - Heparin-binding EGF-like Growth Factor/*biosynthesis MH - MAP Kinase Signaling System/*drug effects MH - MSX1 Transcription Factor/*biosynthesis MH - Mice MH - Mice, Inbred BALB C MH - MicroRNAs/*biosynthesis MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Pregnancy MH - TOR Serine-Threonine Kinases/*biosynthesis MH - Up-Regulation/*drug effects OTO - NOTNLM OT - Calcitonin OT - ERK1/2 OT - HB-EGF OT - Msx.1 OT - mTOR OT - miRNA Let-7a OT - window of implantation EDAT- 2018/09/15 06:00 MHDA- 2019/09/24 06:00 CRDT- 2018/09/15 06:00 PHST- 2018/08/07 00:00 [received] PHST- 2018/09/12 00:00 [accepted] PHST- 2018/09/15 06:00 [pubmed] PHST- 2019/09/24 06:00 [medline] PHST- 2018/09/15 06:00 [entrez] AID - 10.1002/mrd.23061 [doi] PST - ppublish SO - Mol Reprod Dev. 2018 Oct;85(10):790-801. doi: 10.1002/mrd.23061.