Human placental and serum proteins in spontaneous preterm birth

Preterm birth happens before 37 completed weeks of pregnancy. Prematurity is the leading cause of neonatal mortality and morbidity among children under five years of age. Most preterm births are considered spontaneous and half of those do not have an identifiable risk factor. The mechanisms of parturition are not fully understood. However, it is thought that interplay between the mother, the fetus, and the placenta have a role in onset of labor. The aim in this dissertation was to determine placental proteins and their possible roles in spontaneous preterm birth.

We utilized placental proteomics and exome sequencing in the first two studies. After comparing the data sets, two proteins were highlighted: alpha-1 antitrypsin (AAT/SERPINA1), and heat shock protein family A member 5 (HSPA5). In the first study we concluded that the lower expression of placental AAT could affect protein structures in the extracellular matrix of the placenta. These structures have a protective role in immune tolerance between the mother and fetus. Reduced expression of AAT could lead to degradation of these structures weakening the immune tolerance, leading to premature birth. In the second study we proposed that increased amount of HSPA5 may increase the expression of proteins which promote inflammation. This may disturb the inflammatory state of the placenta and lead to preterm birth. In the third study we observed that maternal serum AAT level in early pregnancy was higher in those who gave birth prematurely compared to those who gave birth at term. However, the difference was too modest to use serum AAT as a predictive marker for spontaneous preterm delivery in a clinical setting.

These results give insights in better understanding the pathophysiology of spontaneous preterm birth. The results may help to develop predictive tests as well as novel means to prolong duration of pregnancy.