Renin and angiotensin-converting enzyme 2 expression in the uterus and placenta in immune-dependent and preeclampsia-associated spontaneous abortions in mice
Authors:   Avtsyn Research Institute of Human Morphology of FSBSI Petrovsky National Research Center of Surgery, Moscow, Artemyeva K.A. , Stepanova I.I. ,   Avtsyn Research Institute of Human Morphology of FSBSI Petrovsky National Research Center of Surgery, Moscow, Nizyaeva N.V. ,   Avtsyn Research Institute of Human Morphology of FSBSI Petrovsky National Research Center of Surgery, Moscow, Boltovskaya M.N. ,   Avtsyn Research Institute of Human Morphology of FSBSI Petrovsky National Research Center of Surgery, Moscow, Bogdanova I.M. ,   Avtsyn Research Institute of Human Morphology of FSBSI Petrovsky National Research Center of Surgery, Moscow, Stepanov A.A. ,   Avtsyn Research Institute of Human Morphology of FSBSI Petrovsky National Research Center of Surgery, Moscow, Kondashevskaya M.V. ,   Avtsyn Research Institute of Human Morphology of FSBSI Petrovsky National Research Center of Surgery, Moscow, Ponomarenko E.A. ,   Avtsyn Research Institute of Human Morphology of FSBSI Petrovsky National Research Center of Surgery, Moscow
Published: December 2023

Introduction. Spontaneous abortion and preeclampsia (PE) are the most common pregnancy abnormalities in humans. The renin-angiotensin-aldosterone system (RAAS) and the immune system are among the first to recognize pregnancy and play key roles in its maintenance. RAAS dysfunction is one of the causes of insufficient trophoblast invasion and defect in spiral artery remodeling, which both cause PE. Apart from circulating RAAS components, there are local ones, including uteroplacental ones. The study aimed to analyze the renin and angiotensin-converting enzyme 2 (ACE2) expression in the placenta and uterus in PE-associated spontaneous and immune-dependent abortions in mice. Materials and methods. We reached the physiological pregnancy model by ♀CBA × ♂Balb/c mating (control group); spontaneous PE-associated abortions were ♀CBA × ♂DBA/2. Induced abortions were caused by intraperitoneal β-heptylglycoside muramyldipeptide administration to CBA females fertilized by Balb/c males on gestation days (GDs) 5 and 7. Mice were removed from the experiment on GD 14 after the placenta has completely formed. We performed immunohistochemistry (IHC) of the uterus and placenta using rabbit monoclonal antibodies to renin and ACE2 and evaluated the distribution of the renin- and ACE2-positive cells and the intensity of IHC reaction. Results. Compared to the physiological pregnancy model and immune abortion groups, the spontaneous abortion/PE group was characterized by reduced renin expression in trophoblast giant cells (TGC) and its absence in placental vascular endothelium. We noted increased renin expression in the myometrium and its vascular endothelium in the spontaneous abortion/PE and immune-dependent abortion groups. ACE2 expression in TGC and glycogen cells and placental vascular endothelium was lower in spontaneous/PE and immune-dependent abortions than in the physiological pregnancy group. In contrast, higher ACE2 expression was observed in the myometrium and its vascular endothelium in the abortion groups compared to the controls. Conclusion. Reduced renin expression in TGC and its absence in the placental vascular endothelium of spontaneous abortions/PE group reflects trophoblast invasion disorder characteristic of PE. The detected changes in ACE2 expression in the myometrium in pregnancy failure and PE may represent a systemic compensatory mechanism, which does not exclude the negative effects of renin. Keywords: preeclampsia, pregnancy failure, uterus, placenta, renin-angiotensin-aldosterone system