Calcitonin administration improves endometrial receptivity via regulation of LIF, Muc‐1 and microRNA Let‐7a in mice

• Published in: Journal of cellular physiology 2019-08, Vol.234 (8), p.12989-13000
• Main Authors: Shokrzadeh, Naser, Alivand, Mohammad Reza, Abedelahi, Ali, Hessam Shariati, Mohammad B., Niknafs, Behrooz
• Format: Article
• Language: English
• Subjects: Animals; Calcitonin; Calcitonin - pharmacology; Embryo Implantation - drug effects; Embryo Implantation - physiology; Embryos; Endometrium; Endometrium - drug effects; Endometrium - metabolism; endometrium receptivity; Female; Gene expression; Implantation; implantation window; Injection; Leukemia; Leukemia inhibitory factor; Leukemia Inhibitory Factor - metabolism; mammalian target of rapamycin (mTOR) pathway; Mice; Mice, Inbred BALB C; MicroRNAs; MicroRNAs - metabolism; miRNA; Morphology; Mucin; Mucin-1 - metabolism; Phosphorylation; Pregnancy; Proteins; Rapamycin; Ribonucleic acid; RNA; Signal transduction; Signal Transduction - drug effects; Signaling; Stimulation; Subgroups; TOR protein; TOR Serine-Threonine Kinases - metabolism; Uterus
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.27969

Calcitonin (CT) is one of the factors affecting the embryo implantation, but its effects on the implantation window have not been fully investigated. The current study investigated the effects of CT on the endometrium receptivity by morphological study and evaluation of leukemia inhibitory factor (LIF), mucin 1 (Muc‐1), and microRNA (miRNA) Let‐7a in the ovarian stimulation and the normal ovarian cycle. Then the mechanism of the CT effects through the mammalian target of rapamycin (mTOR) signaling pathway was studied by using PP242. A total of 64 BALB/c mice were divided into the normal ovarian cycle and ovarian stimulation groups. Each group consisted of four subgroups: control, calcitonin, PP242, and calcitonin+PP242. CT and PP242 were injected on the fourth of pregnancy into the mice and 24 hr later all the mice were killed. The uterine tissue samples were used for morphological analysis, and endometrial cells were mechanically isolated for evaluation of gene and protein expression. The results showed that ovarian stimulation induced mTOR phosphorylation as well as increased expression of the Let‐7a miRNA. In addition, CT injection increased the expression of LIF and miRNA Let‐7a in ovarian stimulation similar to that in normal ovarian cycles. However, injection of PP242 reduced expression of miRNA Let‐7a and increased Muc‐1 expression in ovarian stimulation group. In conclusion, the administration of CT improved endometrial receptivity in mice. This phenomenon occurred by upregulation of LIF, miRNA Let‐7a and downregulation of Muc‐1 via mTOR signaling pathway. Calcitonin improves endometrial receptivity via regulation of leukemia inhibitory factor, mucin 1, and microRNA Let‐7a in normal and ovarian stimulation mice.