Estradiol promotes growth of decidua derived mesenchymal stem cells by inhibiting miR-16 via estrogen receptor α

AIM: To study the effect of estradiol (E₂) on the viability of mesenchymal stem cells (MSCs) derived from the decidua of the placenta by regulating the expression of microRNA-16 (miR-16). METHODS: The concentration of E₂ in the peripheral blood of normal pregnant women and the patients with severe preeclampsia (PE) was measured. The effects of E₂ at different concentrations on the viability of MSCs were analyzed. The effect of E₂ at different concentrations on the expression of miR-16 in the MSCs was detected, and which estrogen receptor (ER) mediated the regulatory effect of E₂ on miR-16 expression was determined. RESULTS: The concentration of E₂ in peripheral blood of the patients with severe PE was significantly decreased (P<0.01). After treatment with E₂ at 5, 10 and 100 nmol/L for 48 h, the viability of MSCs was increased (P<0.05). The expression level of miR-16 was down-regulated in the MSCs treated with E₂ at 5, 10 and 100 nmol/L for 12 h. After treatment with E₂ at 10 nmol/L for different time (0 h, 3 h, 6 h, 12 h and 24 h), the expression level of miR-16 in the MSCs showed a clear time-dependent downward trend. E₂ significantly promoted the viability of MSCs, and the cell viability was significantly reversed after miR-16 pretreatment. Pretreatment with estrogen receptor antagonists ICI 182780 and tamoxifen for 6 h attenuated the inhibitory effect of E₂ on miR-16 expression. Only ERα agonist propyl pyrazole triol significantly inhibited the expression of miR-16 in MSCs but ERβ agonist diarylpropionitrile did not. CONCLUSION: E₂ promotes the growth of decidua-derived MSCs by inhibiting miR-16 via ERα.