The different innate immune response to infections in males and females emerges before birth

Abstract

Aim

Sex-specific immune responses to intra-amniotic infections remain poorly understood despite their key role in preterm birth.

Methods

We infected male and female amniotic fluid cells (AFCs) with M. hominis to explore the potential impact of sex-specific innate immune responses, evaluating the gene and protein expression levels of IL-1β, IL-6, IL-8, TNF-α, TLR2 and TLR4, the production of nitrites, and the levels of selected miRNAs.

Key findings

The gene expression of IL-1β, IL-6, IL-8, TNF-α, and TLR2 were elevated in infected females AFCs, while only IL-6, IL-8 and TLR4 expression were up-regulated in infected males. Protein levels of IL-6, TNF-α and TLR2 were up-regulated exclusively in infected females. Furthermore, infected female AFCs produced higher levels of nitrites. MiRNA expression revealed an up-regulation of miR-29a-3p in infected females, and miR-223-3p in infected males, with miR-29b-3p showing up-regulation in both sexes upon infection.

Significance

The response to intrauterine infections differs between males and females. Female foetuses may possess a greater capacity to manage the infection and inflammation, underscoring the importance of personalized prenatal care.