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

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, TLR-2 and TLR-4, 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.