Calcitonin Promotes Mouse Pre‐implantation Development: Involvement of Calcium Mobilization and P38 Mitogen‐Activated Protein Kinase Activation

Abstract

The study was designed to examine the effects of calcitonin (CT) on the development of murine pre-implantation embryos and possible molecular mechanisms involved in the process. In the present study, the 2-cell embryos were treated with different concentration of CT in vitro for the indicated time and the results demonstrated that CT promoted the development of the pre-implantation embryos in a dosage-dependent manner by increasing the intracellular Ca(2+) level. Furthermore, the present study showed that CT significantly increased the expression of phospho-P38MAPK (Mitogen-Activated Protein Kinase) of the pre-implantation embryos by Western blots and pre-treatment of specific P38MAPK inhibitor significantly reduced the promotion effects of CT on the embryonic development in vitro culture. Moreover, the results of intrauterine horn injection showed that the average number of embryos implanted in CT-antibody or specific P38 MAPK inhibitor-treated uterus was significantly lower than that of the corresponding control, respectively. And the observation of tissue specimen suggested that some embryos were degenerated in CT-antibody or specific P38 MAPK inhibitor-treated uterus, and adipose vacuoles were present in the decidual cells. In conclusion, CT promoted the development of pre-implantation embryos and the intracellular Ca(2+) -dependent P38MAPK signal molecule was involved in the process.

The Effects of Calcitonin on the Development of and Ca²⁺ Levels in Heat-shocked Bovine Preimplantation Embryos <i>In Vitro</i>

“…Although the physiological importance of CT in systemic Ca 2+ homeostasis in mammals is controversial [42], the function of CT as a paracrine factor in the female reproductive tract has been suggested [24,25,26]. The expression of CTR mRNA in murine preimplantation embryos has been reported [24], and CT can increase intracellular Ca 2+ levels by activating CTR [24, 25, 43, 44]. Therefore, we examined the expression of CTR mRNA in bovine preimplantation embryos and the effects of CT treatment on the in vitro development of embryos that had been heat shocked.…”

“…Importantly, Wang et al [25] reported that the P38MAPK pathway is partially involved in the enhancing effects of CT on murine preimplantation development in vitro . Therefore, it cannot be excluded that the heat shock-ameliorating effect of CT on bovine preimplantation embryos is also mediated by signal transduction pathways like this that are independent of Ca 2+ signaling.…”

“…The preparation was performed 1 day before use. The concentration of CT (10 nM) in the culture medium was set according to an effective dose for the promotion of Ca 2+ mobilization and preimplantation development of murine embryos [24, 25]. In addition, 10 nM CT was confirmed to be more effective compared with 100 nM in preliminary experiments (data not shown).…”

“…In addition, the mammalian uterus is also a CT producer [22, 23]. Furthermore, murine preimplantation embryos express a functional CT receptor (CTR), and CT has positive effects on the preimplantation development and implantation of these embryos [24,25,26]. These findings suggest that CT is of physiological importance with regard to the female reproductive tract, such that it affects mammalian preimplantation development.…”

“…These findings suggest that CT is of physiological importance with regard to the female reproductive tract, such that it affects mammalian preimplantation development. CT signaling is mediated by an increase in intracellular Ca 2+ in many cell types including preimplantation embryos [24,25,26]. However, the expression profile of CTR and the effects of CT during bovine preimplantation development remain unknown.…”