Antimicrobial proteins and peptides in pregnancy: Guardians of the maternal-fetal frontier

The success of human pregnancy relies on the precise synchronization and adaptation of the maternal immune system, which, together with fetal tissues, establishes a tolerogenic intrauterine environment while maintaining the capacity to mount effective immune responses. At the maternal-fetal interface, multiple physical and immune mechanisms coordinate the recognition and control of pathogens that could jeopardize pregnancy. Ascending infections from the lower genital tract can reach the uterine cavity, infect the fetal membranes (chorioamnionitis), and invade the amniotic fluid, triggering a proinflammatory response strongly associated with adverse outcomes. Both maternal and fetal compartments deploy several defense strategies, among which antimicrobial proteins and peptides (AMPs) play a central role. These small, pleiotropic molecules, produced mainly by epithelial surfaces and inflammatory cells, exhibit broad-spectrum antimicrobial and immunomodulatory activities, constituting a key component of the first line of defense at the maternal-fetal interface. This review summarizes the principal AMPs produced by the placenta, fetal membranes, decidua, maternal reproductive tract, and fetal tissues, describes their mechanisms of action, factors regulating their expression, and explores their role in both physiological and pathological processes.