Trophoblastic epithelial-mesenchymal transition with consecutive fibrosis: a cause for reduced placental function in hyperglycemic pregnancies?

Overall perinatal mortality continues to decline and is currently 0.55 % in Germany. In pregnant women with preexisting diabetes, however, perinatal mortality remains high, despite improved care, and is 1.5 to 2 % in various European studies. Often, sudden failure of placental function occurs close to term, and infants die in utero (Hug 2021). In this case, the usual obstetric monitoring tools are not effective. Histologically, the changes typical of placental insufficiency cannot be detected in these placentas either (Huynh 2014). However, increased fibrosis of these placentas has been demonstrated in a few studies (Salge 2012, Dasgupta 2022, Abdelhalim 2018). Functional studies also show, impaired oxygenation in diabetic placentas (Taricco 2009). Diabetes in pregnancy is associated with persistent maternal hyperglycemia, especially in poorly controlled diabetes, and fibrosis is known to develop in various organs under the influence of hyperglycemia. Functional epithelial tissue is replaced by connective tissue, which is associated with a loss of function. We aim to investigate whether glucose can induce epithelial-mesenchymal transition (EMT) and the development of fibrosis in vitro using trophoblast cell lines and immunohistochemistry in preparations of healthy and type 1 diabetes mellitus placentas.