Exploring the Importance of Differential Expression of Autophagy Markers in Term Placentas from Late-Onset Preeclamptic Pregnancies

Abstract

Preeclampsia (PE) is a serious hypertensive disorder affecting 4–5% of pregnancies globally, leading to maternal and perinatal morbidity and mortality and reducing life expectancy in surviving women post-gestation. Late-onset PE (LO-PE) is a clinical type of PE diagnosed after 34 weeks of gestation, being less severe than the early-onset PE (EO-PE) variant, although both entities have a notable impact on the placenta. Despite the fact that most studies have focused on EO-PE, LO-PE does not deserve less attention since its prevalence is much higher and little is known about the role of the placenta in this pathology. Via RT-qPCR and immunohistochemistry methods, we measured the gene and protein expressions of several macroautophagy markers in the chorionic villi of placentas from women who underwent LO-PE (n = 68) and compared them to normal pregnancies (n = 43). We observed a markedly distinct expression pattern, noticing a significant drop in NUP62 expression and a considerable rise in the gene and protein expressions of ULK1, ATG9A, LC3, ATG5, STX-17, and LAMP-1 in the placentas of women with LO-PE. A major induction of autophagic processes was found in the placental tissue of patients with LO-PE. Abnormal signaling expression of these molecular patterns in this condition aids in the understanding of the complexity of pathophysiology and proposes biomarkers for the clinical management of these patients.

Oxidative Stress, Lipid Peroxidation and Ferroptosis Are Major Pathophysiological Signatures in the Placental Tissue of Women with Late-Onset Preeclampsia

“…Although the causative role of these mechanisms in this variant is unlikely, the literature agrees that the syncytiotrophoblasts from both women with EO-PE and LO-PE exhibit ROS overproduction, oxidative stress, lipid peroxidation and different types of cell death like ferroptosis [45]. Similarly, these processes are tightly linked to other pathophysiological events such as inflammation, hypoxia and autophagy [46,47], whose relevance in the placental tissue of women with LO-PE has been previously demonstrated [11,[48][49][50]. Therefore, our results suggest that oxidative stress, lipid peroxidation and ferroptosis play an important role in the placenta of women with LO-PE, although further efforts are warranted for a better understanding of these mechanisms.…”