Immunology Research Center, Faculty of medicine, Tabriz University Of Medical Sciences, Tabriz, Iran.
Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran.
J Cell Physiol. 2019 Aug;234(8):12989-13000. doi: 10.1002/jcp.27969. Epub 2018 Dec 8.
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.
降钙素 (CT) 是影响胚胎着床的因素之一，但它对着床窗口的影响尚未得到充分研究。本研究通过形态学研究和对白血病抑制因子 (LIF)、黏蛋白 1 (Muc-1) 和微小 RNA (miRNA) Let-7a 的评估，研究了 CT 对卵巢刺激和正常卵巢周期中子宫内膜容受性的影响。然后，通过使用 PP242 研究了 CT 通过哺乳动物雷帕霉素靶蛋白 (mTOR) 信号通路的作用机制。将 64 只 BALB/c 小鼠分为正常卵巢周期和卵巢刺激组。每组分为 4 个亚组：对照组、降钙素组、PP242 组和降钙素+PP242 组。在妊娠第 4 天向小鼠注射 CT 和 PP242，24 小时后处死所有小鼠。使用子宫组织样本进行形态分析，并机械分离子宫内膜细胞以评估基因和蛋白表达。结果表明，卵巢刺激诱导 mTOR 磷酸化，并增加 Let-7a miRNA 的表达。此外，CT 注射增加了卵巢刺激中 LIF 和 miRNA Let-7a 的表达，与正常卵巢周期相似。然而，PP242 的注射降低了卵巢刺激中 miRNA Let-7a 的表达并增加了 Muc-1 的表达。总之，CT 的给药改善了小鼠的子宫内膜容受性。这种现象通过 mTOR 信号通路上调 LIF、miRNA Let-7a 和下调 Muc-1 来实现。
