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Milk Production Can Be “Kick-Started” After a Pause in Breastfeeding – Now We Know How

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A new study from the University of Sheffield has identified a protein that supports milk production after a pause in breastfeeding. The research is published in PLOS Biology.

A fail-safe mechanism for breastmilk production

If an infant has been breastfed, once they progress to solid foods a molecular process commences in the breast tissue. Ultimately, the production of breastmilk winds down, and milk-producing mechanisms are dismantled via cellular suicide, removing the redundant tissue. However, if the infant resumes suckling, this process can be reversed, “kickstarting” breast milk production once again. But how does this occur?

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That’s the focus of a new study from the University of Sheffield, led by Dr. Nasreen Akhtar, lecturer in Developmental Cell Biology in the Department of Oncology and Metabolism. “Despite the massive wave of cell death that occurs in the first phase of the end of lactation, if suckling resumes the breast can reverse the process and re-lactate. This is a fail-safe built-in mechanism to prevent the breast from drying up too quickly,” Akhtar says.

Rac1 a key player for “kickstarting” breast milk production

Akhtar and colleagues utilized mammary glands from mice for their research. This laboratory model is as a suitable choice, the researchers state, due to the structural similarity between mouse and human mammary glands. In mammary epithelial cells (MECS), the researchers found that the presence of a protein called Rac1 causes autophagy – a “cannibalistic” process whereby cells eat their own constituents in an effort to survive.


Some half-dead, half-alive cells experiencing autophagy can be “brought back to life”, enabling milk production once again when the infant suckles on the breast. However, this process can only occur if Rac1 is present. “We have discovered that Rac1 acts as a nexus, controlling both the rate and balance of cell death and progenitor cell division in involution. Without Rac1, cell turnover accelerates with consequences on mammary gland remodelling in the irreversible phase,” the authors write.

Pathways and proteins for the study of breast cancer

The ability of breast tissue to recommence milk production is important for the survival of mammals, Akhtar emphasizes: “If a nursing mammal was separated from her pups for longer than expected whilst foraging, she would still be able feed once reunited.”


“Remarkably some mammals have a really long reversible phase; for example, the cape fur seal, which goes on long offshore foraging trips for up to 28 days can still re-lactate once suckling resumes ashore,” she adds.


In humans, the risk of breast cancer progression is higher in the years following a pregnancy. One proposed mechanism for this increased risk is the altered activity of breast cells during the remodeling processes that occur post-weaning. “The discovery here could expose potential pathways and proteins that cancer cells exploit to survive and grow,” Akhtar concludes.


This article is a rework of a press release issued by the University of Sheffield. Material has been edited for length and content.


Reference: Mironov A, Fisher M, Narayanan P, et al. Rac1 controls cell turnover and reversibility of the involution process in postpartum mammary glands. PLOS Biology. 2023;21(1):e3001583. doi: 10.1371/journal.pbio.3001583.

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Molly Campbell
Molly Campbell
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