Pregnancy permanently rewires rodent intestines

The mother’s body changes in many ways during pregnancy, but still changes a little long after delivery. Researchers at the Francis Crick Institute in London found that pregnancy permanently changes the small intestines of mice, potentially preparing the body for future pregnancy and providing new insights into how organs can adapt to life challenges.

The study was published Wednesday cellreveals that the mice’s small intestine grew by 18% at the end of pregnancy, and surprisingly, even after the mouse has completed care, it will never fully recover its pre-pregnancy size.

This finding marks one of the first detailed studies on how pregnancy affects the digestive system at the molecular and cellular level, which has the potential to increase our understanding of metabolic changes during pregnancy in humans.

“In adulthood rather than early childhood and adolescent development, we don’t often consider organ size or appearance, but the gut is a clear example of how the body responds to new challenges at different stages of life, in which case the gut challenges the body to the body,” said Irene Miguel-Aliaga.

The researchers found that the pregnant woman’s small intestine began to elongate seven days of pregnancy. By day 18 (at the end of the mice’s pregnancy), the intestinal growth was almost one-fifth longer than before pregnancy.

What makes this finding particularly interesting is that even if mice complete care for puppies, the gut is still longer – this change lasts for at least 35 days after weaning. The researchers also observed that the gut grew even longer in the second pregnancy than the first one.

Two-part conversion

The study identified two different types of changes in the intestine: overall extension of the organ and changes in its internal structure.

In the small intestine, there are also significant changes in the finger-like projection called villus (nutrient absorption) and the ups and downs called crypts (cells that produce villus). Both structures grow as the intestine is prolonged during pregnancy, but unlike the permanent increase in intestinal length, these internal structures return to their pre-pregnancy state within one week after weaning.

Researchers believe that these adaptations may enhance nutritional absorption and help mothers support themselves and offspring during pregnancy and care.

To understand what causes these changes, the team digs deeper into the cellular and molecular mechanisms at work.

Cell surge

The team found that in the early stages of pregnancy, precursors of intestinal epithelial cells reproduce rapidly, and newly generated cells migrate faster. The effects of these pregnancy triggers continue through birth and care, but return to pregnancy rates one week after weaning.

By analyzing which genes are activated during pregnancy, the researchers identified a significant change in intestinal cells – nutrients in villus. These changes are mainly associated with increased metabolic activity.

A particularly interesting finding is the early increase in a membrane protein called SGLT3A. Unlike the proteins that sense glucose levels, SGLT3A responds to sodium and protons. The researchers found that the protein causes about 45% of pregnancy-triggered villus growth.

In a revealed experiment, the team found that even in mice that had never been pregnant, simply supplementing the diet of sodium mice could induce villus growth.

Hormonal effects

The researchers observed that even “pseudo-pregnant” mice – women with elevated pregnancy hormone levels after mating with sterile males still showed some gut changes. This suggests that reproductive-triggered hormones may play an important role in initiating these adaptations.

These findings increase our understanding of how female biology adapts to reproductive needs, thus revealing the complex mechanisms that balance energy usage with reproductive success.

“The existence of reversible and irreversible changes may reflect the trade-off of energy,” Miguel-Aliaga explains. “Keeping longer in the gut after the first pregnancy may ‘hit’ the body for a second while reducing the villus length to normal may stop overabsorption without necessity.”

From rats to humans

Although the study was conducted in mice, it raises interesting questions about whether similar changes may occur in humans.

“Understanding how pregnancy affects the bodies of other mammals is a critical first step to understanding people,” said Tomotsune Ameku, a former postdoctoral researcher at Crick, who is now an assistant professor of science in Tokyo and first author of the study.

“We don’t fully understand why the gut expands in response to pregnancy, but we think it must have evolutionary advantages and help mice reappear regularly,” Ameku added.

Researchers point out that modern human lifestyles may change the way these adaptations work. “We usually eat more and reproduce less than before, so the growth of the gut may not be as useful anymore,” Ameku observed.

The team is now studying whether other cell types in the mouse intestine will be remodeled during pregnancy and whether similar changes have occurred in humans. They plan to check the gut length of people who have and have no children to see if there is comparable adaptability in human biology.

This study adds to growing evidence that reproductive events may have lasting effects on female physiology outside of the reproductive system itself—these insights may ultimately help us better understand and address women’s health issues related to metabolism and digestion.