Endocrine Abstracts

The IGF axis is imperative for normal placental development and function. In the human placenta, IGF1R regulates the actions of IGFs and consequently placental growth. Some microRNAs (miRs) are also known to regulate human placental growth. miR-145 is known to exert its effects on human placental growth by targeting IGF1R. Whilst the expression of some components within the IGF axis are similar between mice and humans, murine expression and function of IGF regulatory miRs has yet to be established. We therefore examined the expression of miR-145 and its target IGF1R, and their relationship to growth in the mouse placenta. Placentas from C57 mice were harvested at E12.5, E15.5 and E18.5. At all gestational time-points miR-145 and IGF1R mRNA was assessed by RT-qPCR and normalised to 5srRNA and 18srRNA, respectively. Immunohistochemistry was used to assess IGF1R protein expression. Placental proliferation was assessed by Ki67 immunohistochemistry and subsequent in silico analysis. RT-qPCR demonstrated that miR-145 is expressed in the mouse placenta. miR-145 levels increased with gestation (P<0.05), whilst placental proliferation significantly decreased over gestation (P<0.05). There was no change in placental IGF1R mRNA throughout pregnancy, however, IGF1R protein expression decreased towards term; this discrepancy between mRNA and protein expression is consistent with the known actions of miRs on protein translation. Whilst further work is required to confirm the direct effect of miR-145 in the mouse placenta, this inverse correlation between miR-145 and proliferation/IGF1R is consistent with studies in the human placenta. This suggests that miR-145 is also likely to regulate placental growth in mice by modulating IGF1R expression. Ongoing work will investigate the effect of administering miR-145 regulatory drugs in vivo in mice. If, as expected, effects on placental growth are observed, manipulation of placental miR-145 levels may prove useful to improve pregnancy outcomes associated with aberrant placental development.