# miR-155 suppresses angiotensin II type 1 receptor synthesis during placental morphogenesis

## TL;DR

This study shows that miR-155 suppresses placental development in mice by reducing the production of the angiotensin II type 1 receptor.

## Contribution

The study demonstrates a novel regulatory role of miR-155 in placental morphogenesis through its interaction with AT1R.

## Key findings

- miR-155-/- dams produced heavier pups with larger placental labyrinth zones.
- miR-155-/- placentae showed increased Agtr1 mRNA and AGTR1 protein levels.
- In vitro miR-155 mimic reduced AGTR1 and trophoblast cell activity.

## Abstract

Several microRNAs play vital roles in placental development. miR-155 has been implicated in placental development and can directly interact with a variety of targets, including angiotensin type II receptor 1 (AT1R) (Agtr1) mRNA. The AT1R is pro-proliferative and promotes early placental development. We therefore tested the hypothesis that miR-155 downregulates Agtr1 mRNA expression and impairs placental development. Placentae and fetuses from wild-type C57Bl/6 mice (miR-155+/+, control) and C57Bl/6 mice with a null mutation in miR-155 (miR155-/-) were mated with males of the same genotype and analyzed on gestational day 18.5, when placental morphology and miR-155 and AGTR1 expression were assessed. Additionally, HTR8/SVneo cells were cultured with a miR-155 mimic to determine the effects on trophoblast proliferation, migration and invasion. miR-155-/- dams produced significantly heavier pups with unchanged placental weights and fetal-to-placental weight ratios. Placentae from miR-155-/- dams had significantly larger labyrinth zones and labyrinth-to-placental area ratios than controls, with altered stereological parameters. Placental Agtr1 mRNA and AGTR1 protein levels were significantly increased in miR-155-/- dams. Finally, in vitro treatment in human HTR-8/SVneo cells with the miR-155 mimic increased miR-155 expression, decreased AGTR1 mRNA levels and decreased the rates of trophoblast cell proliferation, migration and invasion. Thus, miR-155 is demonstrated to attenuate placental development in mice. We propose that this is at least partly due to its effects on the AT1R.