Placental autophagy and inflammation in human pregnancy

Abstract

The placenta is a vital organ that establishes a physiological connection between the mother and fetus throughout gestation. Its proper function is essential for fetal development, maternal adaptation, and maintaining a healthy pregnancy. Autophagy and inflammation play key roles in the molecular mechanisms that contribute to placental health and disease, which has wide-reaching implications for reproductive success. This thesis explores the biological background, significance, and interaction of these two processes in human pregnancy. It highlights their roles in normal physiology and their contribution to pregnancy-related complications. The text discusses the structure and function of the human placenta, emphasizing its roles in nutrient exchange, hormone production, immune modulation, and waste elimination. Understanding its architecture is essential for investigating how molecular mechanisms affect placental performance. Autophagy is a cellular degradation process that is essential for adapting to stress and removing damaged organelles. Placental autophagy is shown to be essential for cellular homeostasis, trophoblast differentiation, and adaptation to hypoxic and metabolic stress. Defective autophagy has also been linked to placental dysfunction and disorders such as preeclampsia and intrauterine growth restriction (IUGR). Along these lines, the inflammatory landscape of the placenta is discussed. While localized, controlled inflammation is a normal part of implantation and labor, uncontrolled or chronic inflammation can cause harm. The placenta must balance maternal immune tolerance with protective immune responses, a process mediated by cytokines, immune cells, and trophoblast signaling. An imbalance can disrupt placental function and contribute to adverse pregnancy outcomes. The central findings are presented in the Results section, which highlights the interplay between autophagy and inflammation in the placenta and their impact on pregnancy-related complications. The results demonstrate that autophagy can modulate inflammatory responses. Conversely, excessive inflammation can impair autophagic flux, resulting in trophoblast dysfunction. This bidirectional relationship is particularly significant in the context of pregnancy complications. In conclusion, coordinated autophagy and immune responses are essential for healthy placental function. Disturbances of these processes may underlie major obstetric disorders. Further research offers potential targets for future diagnostic and therapeutic approaches.

Date of Award	2025
Original language	English
Awarding Institution	Medical University Graz
Supervisor	Martin Gauster (Supervisor) & Gerit Moser (Co-supervisor)