Molecular Mechanisms Underlying Twin-to-Twin Transfusion Syndrome

Abstract

Twin-to-twin transfusion syndrome is a unique disease and a serious complication occurring in 10–15% of monochorionic multiple pregnancies with various placental complications, including hypoxia, anemia, increased oxidative stress, and ischemia-reperfusion injury. Fetoscopic laser photocoagulation, a minimally invasive surgical procedure, seals the placental vascular anastomoses between twins and dramatically improves the survival rates in twin-to-twin transfusion syndrome. However, fetal demise still occurs, suggesting the presence of causes other than placental vascular anastomoses. Placental insufficiency is considered as the main cause of fetal demise in such cases; however, little is known about its underlying molecular mechanisms. Indeed, the further association of the pathogenic mechanisms involved in twin-to-twin transfusion syndrome placenta with several molecules and pathways, such as vascular endothelial growth factor and the renin–angiotensin system, makes it difficult to understand the underlying pathological conditions. Currently, there are no effective strategies focusing on these mechanisms in clinical practice. Certain types of cell death due to oxidative stress might be occurring in the placenta, and elucidation of the molecular mechanism underlying this cell death can help manage and prevent it. This review reports on the molecular mechanisms underlying the development of twin-to-twin transfusion syndrome for effective management and prevention of fetal demise after fetoscopic laser photocoagulation.

RAAS-Deficient Organoids Reveal that Delayed Angiogenesis Is The Pathomechanism Underlying Autosomal Recessive Renal Tubular Dysplasia

“…In the kidney, some reviewers discussed this connection 27,28 , but mostly in the context of rodent physiology which is less sensitive to this delay and does not display the RTD phenotype following RAAS disruption. Given that murine kidney surface area is signi cantly smaller than in humans, a lower concentration of angiogenic factors may still reach the necessary threshold needed for su cient cortical vasculature recruitment and subsequent normal PT development 56,57 . While the RAAS-VEGF mechanism explains PT loss in both inherited (AR-RTD) and acquired (e.g.…”

RAAS-deficient organoids indicate delayed angiogenesis as a possible cause for autosomal recessive renal tubular dysgenesis

“…While the RAAS-VEGF mechanism explains PT loss in both inherited (AR-RTD) and acquired (e.g., ACE inhibitors/ARBs during pregnancy) forms of the disease 19 , 21 it is not yet clear how RTD develops in the donor twin in TTTS or in fetuses with congenital cardiac malformations. Studies of TTTS suggest a significant role for both RAAS and angiogenic misregulation 67 . Hence, even though AngII is present, TTTS/congenital heart disease may experience delayed tubular vasculogenesis and subsequent RV/SSB starvation for other reasons, resulting an RTD-like phenotype.…”

Monochorionic twin pregnancy from the perspective of the theory of complexity

“…• Complex systems encompass dynamism: 2 pregnancy is dynamic and a normal checkup does not warrant that the same conditions will be found the next day. Interactions occur at different levels on a continuous basis: from a microvascular and molecular level 15 to a macro mother-fetus level; conditions vary continuously. Such imbalance 2 or dynamic balance actually allows a rapid adaptation to different stimuli.…”