Abstract

Antimicrobial peptides (AMPs) are short cationic amphipathic peptides with a wide range of antimicrobial properties and play an important role in the maintenance of immune homeostasis by modulating immune responses in the reproductive tract. As intra-amniotic infection and microbial dysbiosis emerge as common causes of preterm births (PTBs), a better understanding of the AMPs involved in the development of PTB is essential. The altered expression of AMPs has been reported in PTB-related clinical presentations, such as preterm labor, intra-amniotic infection/inflammation, premature rupture of membranes, and cervical insufficiency. Moreover, it was previously reported that dysregulation of AMPs may affect the pregnancy prognosis. This review aims to describe the expression of AMPs associated with PTBs and to provide new perspectives on the role of AMPs in PTB.

Highlights

  • Preterm birth (PTB) refers to a multi-etiological condition that occurs in more than one out of ten child births, and approximately 1.1 million neonates die from prematurity-related complications each year [1]

  • Considering that microorganisms frequently found in intra-amniotic infection are common constituents of vaginal microbiome, intrauterine infection could often be a result of ascending infection by lower genital tract microorganisms [15,16,17]

  • Recent studies have shown that Lactobacillus iners-dominant vaginal communities (CST III) are associated with PTB, and vaginal dysbiosis characterized by lower levels of Lactobacillus spp. and high species diversity, as in bacterial vaginosis (BV), has been associated with increased risk of premature rupture of membranes (PPROM), PTB, and histologic chorioamnionitis [39,94,115,116]

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Summary

Introduction

Preterm birth (PTB) refers to a multi-etiological condition that occurs in more than one out of ten child births, and approximately 1.1 million neonates die from prematurity-related complications each year [1]. The key mechanism of the antimicrobial action of AMPs involves the formation of an amphipathic secondary structure upon contact with cytoplasmic membranes, which leads to membrane perturbation, bacterial cell content leakage, and cell death [70,71]. Mammalian cell membranes generally consist of zwitterionic phospholipids and have a neutral net charge, wherein phospholipids with negatively charged head groups face inward [49,73,74] This results in a relatively weak hydrophobic interaction with AMPs, and the high cholesterol content in mammalian cell membranes reduces AMP activity by stabilizing the phospholipid bilayer [49,75]. AMPs exhibit antiviral activity by destabilizing the viral envelope and damaging the virions, or inhibiting the viral replication of non-enveloped viruses to prevent the nuclear entry of the viral genome [76,77,78]

Immunoregulatory Functions of AMPs
AMP-Microbiome Interaction
Expression of AMPs in Pregnancy
AMPs Associated with PTB
Findings
Conclusions and Future Perspectives
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