Being a new mum comes with a whole host of weird, wonderful, and often uncomfortably rapid physical changes, but one of the most remarkable has to be the transition of breasts from ordinary lumps of mammary tissue to 24-hour milk machines – and then back to normal again just as fast.
The fact that this transition can occur in a matter of days has been a tough one for biologists to explain, but a new study finally has some answers. Scientists have identified a cellular process that causes breast cells to transition from milk secretors to cannibals.
Pregnancy and the months that follow childbirth are no picnic for a woman’s body, but there’s one thing we can be grateful for – the fact that when the breasts stop producing milk, the body doesn’t respond the way it normally would when there’s a bunch of dead cells lying around.
Under normal circumstances, when your body has a bunch of junk to clean up – such as bacteria, foreign matter, or dead or dying red blood cells – cells called phagocytes swoop in and ingest them, clearing away any unwanted build-up or infections.
But when a woman stops breastfeeding, specialised ‘epithelial cells‘ that form tiny milk-secreting sacs called alveoli self-destruct in huge numbers to allow the breasts to return to their regular state, and scientists have struggled to explain how phagocyctes alone could clean all of this up so painlessly.
As Linda Geddes explains for New Scientist, if phagocyctes alone were responsible for clearing away the huge amounts of dead cells and surplus milk that result from the end of breast-feeding, it would be an incredibly uncomfortable experience for new mums.
“[T]he body’s immune cells usually remove dead and dying cells through a process called phagocytosis, yet the amount of material that is consumed is so great, that you’d expect significant inflammation, pain and tissue damage – something that doesn’t typically happen when breastfeeding ceases,” says Geddes.
“One of the least understood aspects of this process is how the excess milk and large numbers of dead cells are removed from the mammary gland without substantial activation of the immune system,” Matthew Naylor, a cancer biologist at the University of Sydney in Australia, who wasn’t involved in the research, told her.
A team led by Nasreen Akhtar from the University of Sheffield in the UK decided to investigate.
They’d already singled out the protein they wanted to focus on – Rac1, which plays a key role in milk production, but also in phagocytosis. They bred mice that were unable to produce the Rac1 protein, and observed what happened when they had pups.
The first litter of pups survived, but they were much smaller than normal, and all other subsequent litters died.
The team found that dead cells and excess milk from the first pregnancy had clogged up the breast tissue, causing such severe inflammation and swelling that the mice were unable to produce enough milk to feed their new litters.
“Without Rac1, the dead cells and milk flood the interconnecting breast ducts causing them to bloat and triggering chronic inflammation,” Akhtar explains in a press release. “The bloated ducts then fail to regenerate and produce milk in a future pregnancy.”
This is the first time it’s been demonstrated that Rac1 is not just involved in phagocytic activity – it’s crucial for it to happen at all.
And it turns out that when it’s facilitating phagocytosis in breast tissue, Rac1 also appears to keep dead or dying epithelial cells attached to the alveoli for longer, and this could encourage them to eat each other, rather than getting the immune cells involved.
The research isn’t just of interest to curious mothers – it could help us understand how we shed the equivalent of our own body weight in dead cells every year.
“If immune phagocytes were the only cell type to clear up cell corpses our bodies would be continuously inflamed. It’s quite likely that epithelial engulfment occurs in many other organs, because this cell type forms the building blocks of our bodies,” Ahktar explains in the release.
It could also help us figure out why certain cells become cancerous, because those epithelial cells that are eating each other at the alveoli when breastfeeding ends are the same types of cells that over 90 percent of cancers come from.
And that’s important news for researchers working on anti-cancer therapies based on Rac1.
“Rac1 is over-expressed in various cancers including breast cancer and Rac1 inhibitors are currently being considered as anticancer therapies,” says Ahktar. ” But given that sustained inflammation is linked to cancer progression, the findings show that blocking Rac1 might not be a good idea.”
The results have been published in Developmental Cell.