MicroRNA-210 regulates placental adaptation to maternal hypoxic stress during pregnancy†

MicroRNA (miR)-210 is a well-known hypoxia-inducible small RNA. Increasing in vitro evidence demonstrates its involvement in regulating multiple behaviors of placental trophoblasts. However, direct in vivo evidence remains lacking. In the present study, we generated a miR-210-deficient mouse strain using CRISPR/Cas9 technology, in which miR-210 expression was markedly deficient in various tissues. Little influence on fertility rate and litter size was observed after the deletion of miR-210 in mice. Continuous exposure of pregnant mice to hypoxia (10.5% O2) from E6.5 to E10.5 or to E18.5 led to reduction in fetal weight, and such fetal weight loss was markedly worsened in miR-210-knockout dams. Analysis of the placental structure demonstrated the reduced expansion of placental spongiotrophoblast layer and hampered development of labyrinth fetal blood vessels in knockout mice compared to the wild-type controls upon hypoxia stimulation. The findings indicate that miR-210 participates in regulating placental adaptation to hypoxic stress during pregnancy.