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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
Author(s) -
Shokrzadeh Naser,
Alivand Mohammad Reza,
Abedelahi Ali,
Hessam Shariati Mohammad Bakhtiar,
Niknafs Behrooz
Publication year - 2018
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.23061
Subject(s) - calcitonin , endometrium , endocrinology , biology , medicine , downregulation and upregulation , pi3k/akt/mtor pathway , stromal cell , stimulation , ovary , andrology , signal transduction , microbiology and biotechnology , gene , biochemistry
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.