Female gut muscles reshape to meet the demands of reproduction, preclinical study suggests

by The Francis Crick Institute

edited by Lisa Lock, reviewed by Robert Egan

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Organs don't just grow in early life; they can change in response to physiological or environmental challenges in adulthood. Researchers have now identified an active role for the intestinal muscles in remodeling the gut after reproduction.

Crick developmental biologist Irene Miguel-Aliaga is interested in how organs like the intestine change throughout life and whether there are differences between male and female animals. Her team recently found that fruit fly and mouse intestines grow in females in response to reproduction and that this is necessary to sustain their offspring, possibly by increasing nutrient intake.

The researchers had assumed these changes occurred only in the intestinal lining, which responds to hormone fluctuations during reproduction. Much less was known about the role of the intestinal smooth muscle that lines the gut.

"We know skeletal muscles change in response to nutrients or the environment: these are the muscles that grow when you exercise them in the gym," says Miguel-Aliaga. "Visceral muscles cover our organs like the lungs, intestines and bladder, contract slowly and are not consciously controlled. We wanted to know if the intestinal muscles play a passive mechanical role or are actively influencing a change in gut length in response to reproduction—and whether this is sex-specific."

Muscle power

In research published August 11 in the journal Cell, Alessandro Mineo, a postdoctoral researcher on Miguel-Aliaga's team, used imaging techniques to compare muscle cells in male and female fruit flies. He found that intestinal muscles are intrinsically different in males and females, with females having thicker and more numerous muscle cells. In contrast, intestinal muscles in male and female mice were similar in thickness and number before mating.

But reproduction had striking effects in both species. "Despite fruit flies laying eggs and mice giving birth, it was the same story in females of both animals: The intestinal muscles visibly changed after mating," Mineo says. "We didn't see this in males."

This change manifested as growth of the muscle filaments—the parts that make the muscle contract—rather than an increased number of muscle cells. This made the muscles longer and less contractile. "We think slower contractions allow the gut to absorb more nutrients, rather than pushing food through quicker," Mineo says. "This could help meet the energy demand to produce eggs in flies or for lactation in mice."

Unraveling the layers of sex differences

Miguel-Aliaga and Mineo next set out to understand what makes female muscles specifically responsive to reproduction.

"We switched on sex-specific genes in the intestinal muscles in fruit flies, so the muscle cells had a different sex from the rest of the fly," Mineo explains. "This resulted in the muscles becoming more 'male' or 'female,' depending on which genes were expressed, showing that intestinal muscles have an intrinsic sexual fate that affects their length and thickness."

But muscle growth still occurred in females with altered "male" gut cells after reproduction, suggesting to the team that there must be another layer of control beyond biological sex.

They had previously shown that post-mating growth of the entire intestine results from activation of a hormone called Juvenile Hormone (JH) in epithelial cells. When they examined JH signaling in the intestinal muscles, they found a surprising contrast: While JH promotes growth in epithelial cells, reduced JH signaling in muscle cells encouraged the muscles to grow.

They also observed that intestinal muscles respond to mating by reducing the number of JH receptors on their surface, making them less sensitive to the hormone. Together, these findings suggest that JH normally restrains remodeling in the muscle layer and that making muscles insensitive to JH allows them to ease off this restraint and adjust their size and function after reproduction.

"We think this is because the muscles are the gatekeepers to remodeling the gut," Mineo says. "They can adapt in response to pregnancy but also to changes in nutrition or the immune system: They're integrating both types of information. This makes the process flexible; it's not a switch that's constantly left on."

Maintaining energy balance

Another key part of Miguel-Aliaga's work is examining whether these patterns of organ change are also evident in people. Humans don't have JH, but she thinks a plausible candidate for muscle growth is thyroid hormone, which has been shown to increase during pregnancy. Other hormones that affect smooth muscle, like progesterone, might also be involved.

"The intestine balances energy in and energy out," says Miguel-Aliaga. "Building bigger and less contractile muscles might help extract more nutrients during reproduction, when energy is needed for laying eggs or lactation. But it's a bit of a double-edged sword: If gut muscles fail to return to a post-reproductive state, we're thinking about whether this might lead to weight retention after giving birth."

If the same mechanisms exist in humans, Miguel-Aliaga believes targeting intestinal muscle plasticity might be a way to restore energy balance after a physiological challenge like pregnancy.

Alongside continuing its investigations into sex-specific gut changes in flies and mice, Miguel-Aliaga's team is now beginning research involving people who have or haven't had children to understand the implications of reproduction for our own intestines.

Publication details

Alessandro Mineo et al, The sex and reproductive plasticity of intestinal muscles instruct gut size, Cell (2026). DOI: 10.1016/j.cell.2026.07.024

Journal information: Cell

Clinical categories

GastroenterologyWomen's healthObstetrics & gynecologyDigestive healthPregnancy Provided by The Francis Crick Institute Who's behind this story?

Lisa Lock

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