Angiotensin II type 1 receptor has impact on murine placentation.
Impaired placentation is a key step in the pathogenesis of important pregnancy disorders such as preeclampsia and fetal growth restriction. A role of angiotensin II in placental development can be assumed from the expression of angiotensin receptors on trophoblast from the earliest stages of pregnancy. To understand the role of angiotensin II type 1 (AT1) receptors in placental development, we investigated placentae of AT1a-deficient mice early in pregnancy (day 13 postconception). The number of alive newborns was significantly reduced in AT1a-deficient mice caused by placental malformations in 30% of all utero-placental units. Importantly, no embryonic structure was observable within the uterine segments harboring the malformed placentae. Immunohistochemistry with an antibody against murine betahCG-equivalent stained homogeneously in almost all cells in the altered placentae indicating still an endocrine-active trophoblast. However, the typical structure of the murine wild-type placenta in spongiotrophoblast, giant cells, and labyrinth was abolished in malformed placental tissue deficient in the AT1a receptor. Recent epidemiological studies revealed the detrimental effect of an AT1 blockade for fetal outcome due to renal malformations and a reduced birth weight. For the latter, our findings provide an early mechanistic explanation. The lack in AT1 stimulation causes an impaired trophoblast maturation leading to impaired placental function.
Walther
T
T
Department of Cardiology and Pneumology, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin, Germany. thomas.walther@hyms.ac.uk
Jank
A
A
Heringer-Walther
S
S
Horn
L-C
LC
Stepan
H
H
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000502:physiology*; D000818:Animals; D005260:Female; D008098:Litter Size; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010920:Placenta / Q000473:pathology / Q000502:physiology*; D010929:Placentation; D011247:Pregnancy; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C119712:Agtrap protein, mouse; D044140:Receptor, Angiotensin, Type 1