Aim. The placenta is a vital organ connecting mother and fetus, crucial for fetal development and maternal adaptation. Dysregulation can lead to the pregnancy complications, yet understanding of gene expression changes during normal pregnancy is limited. This study examines the 30 most statistically significant biological processes in which genes show coordinated and most pronounced changes in expression in the placenta between the I and II trimester of physiological pregnancy. Conclusions. The transition from the first to the second trimester is characterized by dynamic immune tolerance, balancing immune activation and deactivation to protect the fetus and maintain a healthy placental environment. The study’s findings highlight the key genes and pathways that influence placental function and fetal development, particularly in early pregnancy stages where complications often arise.