The foundations of eczema may start to be laid down in the womb

Stress during pregnancy, perhaps around the 6-to-8-month mark especially, may prime certain immune cells in a fetus’s skin to overreact, leading to eczema.

Immune cells called mast cells in the skin release histamine and other chemicals that trigger redness, swelling and itching during allergic reactions. Eczema isn’t a type of allergy, but these same chemicals can help fuel the inflammatory flare-ups it induces in response to irritating, rough or damp substances, like soap, washing detergent and diapers.

A series of experiments on mice has now shown that mast cells become hyperreactive when a fetus is exposed to stress hormones in the uterus.

“Something our work really brings out is that pregnant women’s emotional experiences can indeed have an impact on their children’s health,” says Nicolas Gaudenzio at the Toulouse Institute for Infectious and Inflammatory Diseases in France. “Making mothers feel guilty is absolutely not the point of this research. Maybe this is more of a message for women’s partners and their support systems.”

Previous research has suggested there is a link between stress during pregnancy and eczema in newborns. To understand the mechanisms behind this, Gaudenzio and his colleagues ran experiments on dozens of pregnant mice.

Some were put under stress by being placed in narrow tubes with bright lights shining on them for half an hour, three times a day for five days. The researchers specifically targeted the late second and early third trimesters, a critical window for the development of the immune and nervous systems. They found that the mice’s stress hormone levels spiked in both the bloodstream and the amniotic fluid during this period.

After the pups were born, the researchers either mimicked the wearing of diapers by placing pads soaked in saline on their backs or gently rubbed adhesive tape behind their knees and in the bends of their elbows – typical eczema hotspots.

They found that nearly all the offspring of the stressed mothers developed eczema-like rashes that were red, itchy or scaly at those sites, while those born to control mothers – which were free to roam in a cage during pregnancy – sometimes showed mild irritation, but never full-blown lesions.

RNA sequencing of the sensory neurons linking the skin to the spinal cord revealed that nearly 300 genes were expressed differently in the offspring of the stressed mice, many of which are tied to pain, touch and itching, suggesting heightened skin sensitivity. The pups born to stressed mothers also reacted much more strongly to gentle contact, like being brushed with fine nylon filaments.

Sequencing of immune cells from the pups’ skin showed 500 differently expressed genes in the mast cells. Under a microscope, these looked as if they were gearing up to release histamine. “They were already active at rest, in a neutral environment, which means the skin is predisposed to develop inflammation,” says Gaudenzio.

The researchers repeated their experiments in pregnant mice treated with drugs that prevent them from creating corticosterone, a hormone that plays an important role in the stress response in rodents, and those pups didn’t have eczema. They also gave extra corticosterone to pregnant mice that weren’t in stressful situations – their pups did develop eczema.

The researchers then genetically engineered pups to lack mast cells altogether. Those animals didn’t develop eczema, even when their mothers had been stressed.

“It’s quite a thorough and very interesting study,” says Thomas Plum, who specialises in cellular immunology at the German Cancer Research Center in Heidelberg. “It underlines this new view in the field that, at the tissue level, interactions between immune cells, structural cells and the nervous system are everywhere and play really important roles.”

Even so, it is important to keep in mind that the experiments were done on mice. “It’s intriguing, but it’s just the first foot in the door,” says Plum.