Maternal stress triggers early-life eczema through fetal mast cell programming
- zeemfindsout
- Mar 22
- 3 min read
The big idea:
The effect of prenatal stress (PS) on atopic dermatitis at birth was investigated and was found to induce fluctuations in maternal hormones.
This resulted in dysregulations in the fetal immune system, leading to altered mast cell and sensory neuron function, which predisposes offspring to develop eczema as a response to typically harmless friction on skin after birth.
What the study asked:
Considering that previous studies suggested an association between PS and heightened risk of eczema in children but did not identify the biological mechanisms that lead to such observations, this study sought to show that eczema at birth originates from molecular dysregulation in the fetal immune systems before birth.
What the study did:
A non-infectious mouse model of PS was used for this study, where:
Pregnant mice were restrained and exposed to bright light for 30 minutes, 3 times a day for 5 days.
The offspring of the mice were then investigated at various stages.
At 8 weeks, the serum of offspring was studied for its protein concentrations in comparison to control (CT) offspring.
Since paediatric atopic dermatitis usually develops in areas exposed to continuous mechanical skin damage, a model of tape stripping was used to replicate its impacts.
This model is known not to induce signs of inflammation in offspring.
3 complementary experiments were also carried out to compare the mechanical sensitivity of PS offspring as compared to CT offspring.
This is as increased mechanical sensory sensitivity is an important factor that participates in the full spectrum of discomfort experienced by children with atopic dermatitis.
Further experiments were also done to explore the specifics of how various neurons are affected by PS.
The molecular impacts of stress during gestation on immune cells in the skin, such as mast cells (specialised immune cells found throughout the body's connective tissues) was also investigated through various experiments on isolated specific immune cells.
The role of mast cells in PS-associated eczematous lesions in response to the model of light continuous wet friction was also investigated.
What the study found:
Using the mouse model of PS, the skin of 8-week-old PS offspring was similar to that of CT offspring in terms of visuals and abundance of key barrier proteins.
However, both week 3 and week 8 PS offspring displayed a relatively high rate of water loss across the skin.
This is a well known indicator of loose barrier in atopic dermatitis, especially in children, indicating that although PS offspring appear to have normal skin, subtle alterations in skin barrier are present.
In response to the test using mechanical damage, both week 3 and week 8 offspring rapidly developed eczematous lesions which revealed pronounced inflammation.
After light but continuous wet friction was induced, the PS offspring rapidly developed severe lesions with outbreaks of eczema with a significant increase in epidermal thickness while the CT offspring did not show any signs of inflammation.
At 24 weeks, PS offspring displayed only a quickly resolving dryness, without any signs of eczematous lesions or epidermal thickening.
Hence, these data demonstrate that this model of PS is associated with the development of eczema-like lesions in children in response to otherwise harmless mechanical friction.
The lesions exhibit different pathological features than adult atopic dermatitis, and the symptoms can naturally resolve with age.
From the experiments on mechanical sensitivity, it was found that:
PS offspring displayed significantly higher sensitivity than CT offspring in all tested behavioural experiments.
Results also showed that PS was associated with modifications in neuronal compartments as well as with abnormal responsiveness to mechanical stimuli.
Skin mast cells from PS offspring were already highly activated, and PS-associated eczematous lesions in response to light wet friction were found to depend on the dysregulation of certain skin mast cells for full development.
However, such dysregulations were no longer present in skin mast cells isolated at week 24.
What this means for eczema:
The study introduces a new concept where early-onset eczema could have a prenatal origin, which promotes a deeper understanding of how mothers can impact their children before birth.
This can lead to new interventions to alleviate the impacts of environmental factors during pregnancy, with the end goal of reducing the extremely high incidence of paediatric eczema and eventually other allergic disorders.
Link to study:
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