Key result
miR-155 deficiency in mice increases AGTR1 levels, driving larger placental labyrinth zones and heavier pups.
Why the study?
miR-155 is implicated in placental development and targets AT1R, a pro-proliferative receptor that promotes early placental development, prompting the hypothesis that miR-155 downregulates Agtr1 and impairs placental development.
miR-155 suppresses angiotensin II type 1 receptor synthesis and attenuates placental development in mice.
Should not yet change obstetric practice; leaves open miR-155 as a regulator of placental and fetal growth for human validation.
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 (AT 1 R) ( Agtr1 ) mRNA. The AT 1 R 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 AT 1 R.
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Arthurs et al. (2025) studied this question. miR-155 deficiency in mice resulted in increased Agtr1 mRNA and AGTR1 protein levels, leading to larger labyrinth zones in placentae and heavier pups without weight gain.
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