miR223-3p, HAND2, and LIF expression regulated by calcitonin in the ERK1/2-mTOR pathway during the implantation window in the endometrium of mice.

Problem: Approximately one-third of infertility cases are related to the female partner, and implantation failure is the primary reason for female infertility. The current research was established to assess the impact of calcitonin on endometrial receptivity.

Methods Of Study: 64 female BALB/c mice were assigned to 2 groups as follows: mice with regular ovarian cycle and mice with stimulated ovarian cycle. The two groups were further divided into four subgroups as follows: control (Ctrl), calcitonin (CT), pp242, and CT + pp242 groups. Calcitonin and pp242 were injected on days 3, 4, and 5 of pregnancy. On day 5 of gestation, all of the animals were sacrificed, and their uterine was removed for the morphological analysis, as well as the expression assessment genes and proteins.

Results: The results demonstrated that ovarian stimulation increased the rate of phosphorylation of ERK1/2 and mTOR proteins, and resulted in the upregulation of miR-223-3p. The administration of calcitonin also elevated the expression levels of LIF and HAND2 gene in both regular ovarian and ovarian-stimulated cycles. In ovarian-stimulated groups, the administration of calcitonin led to a decrease in the expression of miR-223-3p. Calcitonin administration also markedly increased the phosphorylation of 4EBP1 and ERK1/2 in the regular ovarian cycle.

Conclusion: It seems that calcitonin is capable of enhancing the endometrial receptivity of the uterine, thereby the overexpression of HAND2 and LIF and downregulation of miR-223-3p through the ERK1/2-mTOR signaling pathway.