The study published in the American Journal of Physiology-Gastrointestinal and Liver Physiology explores the interplay between genetic and environmental factors during pregnancy and its influence on inflammatory diseases postnatally, including Eosinophilic Oesophagitis (EoE), a chronic allergic disease triggered by food. 

Researchers focused on the effects of amniotic fluid (AF), the protective liquid surrounding a baby in the womb, on the development of oesophageal cells and their response to allergic stimuli.

Illustration from American Journal of Physiology-Gastrointestinal and Liver Physiology, showing how amniotic fluid influences oesophagal development and inflammation, with implications for Eosinophilic Oesophagitis (EoE). Source

Key Findings:

Using a technique called multiplex analysis, researchers identified 66 cytokines in AF. Cytokines are small proteins that help immune cells communicate and trigger immune responses.

Interestingly, two cytokines central to allergic inflammation pathways —IL-4 and thymic stromal lymphopoietin (TSLP)—were missing from the fluid.

The analysis also revealed differences based on pregnancy outcomes. In preterm births, AF contained high levels of proinflammatory cytokines, such as TNFα and IL-12, linked to inflammation. In contrast, AF from term births had the highest epidermal growth factor (EGF) levels, a molecule essential for tissue development and healing.

When oesophagal epithelial cells were exposed to AF, it resulted in transient phosphorylation (temporary activation) of a signalling pathway known as ERK1/2. This signalling pathway plays a key role in regulating cell growth, differentiation, and responses to environmental stimuli.

This activation led to the transcription of early response genes, demonstrating that AF directly influences the behaviour and development of these cells.

Using a three-dimensional spheroid model, researchers found that AF altered the normal process by which oesophagal cells mature and organise, known as the differentiation program. Additionally, it enhanced the transcription of IL-13-target genes, including CCL26, which attracts eosinophils and CAPN14, which encodes for a major genetic susceptibility locus for eosinophilic oesophagitis.

The study found that the gene CAPN14 was significantly upregulated in the 3D oesophagal spheroid models when exposed to preterm AF.

However, this upregulation did not occur when the spheroids were exposed to term AF.

Conclusions

In summary, the findings highlight AF as an important factor in shaping the intrauterine environment, potentially influencing the development of oesophagal disorders later in life.

The interaction between AF and the oesophagal lining during pregnancy plays a crucial role in shaping how oesophageal cells develop and respond to inflammation, particularly to interleukin 13 (IL-13). This process may increase the risk of developing inflammatory oesophageal conditions, like EoE, later in life.

Read the full publication.

Rochman, M., Klinger, A. M., Caldwell, J. M., Sadovsky, Y., & Rothenberg, M. E. (2024). Amniotic fluid modifies esophageal epithelium differentiation and inflammatory responses. American Journal of Physiology-Gastrointestinal and Liver Physiology. https://doi.org/GI-00197-2024

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