Evaluation of calcitonin effects on endometrial receptivity markers during implantation window in mice

Abstract

This study aimed to evaluate calcitonin effects on endometrial receptivity. To this end, the effects of calcitonin on the endometrial receptivity were investigated by the histomorphological study of the endometrium as well as the expression of LIF,Muc1, HAND2, MSX.1, HB-EGF and miRNA Let-7a. The mTOR and ERK1/2 signaling pathways were evaluated by using inhibitor of mTOR pathway(PP242). 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 4 subgroups: Ctrl, CT, PP242, and CT+PP242. Calcitonin and PP242 were injected on the 4th of pregnancy and 24 hours later all the mice were sacrificed. Uterine tissue samples were used for histochemical analysis with PAS.Also,the endometrial epithelial and the stromal cells were isolated for evaluating proteins and genes expression. Results: Calcitonin led to epithelial cells transformation form to cuboidal and also proliferation in stromal cells in both ovarian stimulation and normal mice. However, PP242 injection in ovarian stimulation and normal miceresulted epithelial transformation form to columnar. Ovarian stimulation increased the p-mTOR and p-ERK1/2 and the expression of miRNA let-7a. Calcitonin increased the expression of LIF, HAND2, HB-EGF, Msx.1, and miRNA Let-7a in a normal and ovarian stimulated mice. It also increased p-4EBP1 andp-ERK1/2 in normal mice. Also, injection of PP242 inhibited p-mTOR and p-4EBP1 phosphorylation in both groups.It also reduced expression of miRNA Let-7a in ovarian stimulation mice but increased Muc1 expression in both groups.