Cambridge Researchers Map Gene Activity in Mammary Glands
Mammary glands are specialized glands in mammals whose primary function is to produce and secrete milk to feed their offspring. They begin developing during puberty, but their most significant growth and functional maturation occur during pregnancy. They contain different types of cells, each with its own function. However, the question is: how do these cells change during processes such as breastfeeding, or what genetic changes occur?
Over the decades, research has greatly expanded our understanding of breastfeeding. For example, oxytocin was first discovered in 1906, and prolactin in 1928. Prolactin stimulates milk production, while oxytocin plays a role in the release of milk during breastfeeding.
More than 100 years after
More than 100 years after the discovery of these hormones, scientists have created the most detailed atlas of gene expression ever produced for the developmental cycle of the mammary gland. They have identified new genes involved in breastfeeding, as well as how genetic changes are linked to breastfeeding disorders and postpartum breast cancer.
A University of Cambridge study investigated the cellular composition of the mammary gland at key stages: before the first pregnancy, throughout pregnancy, during breastfeeding, and during involution (the process by which the tissue returns to a resting state).
The study titled, Dynamic allelic expression in mouse mammary glands across the adult developmental cycle was published in the journal Nucleic Acids Research. As they stated: “Our results provide a global, unbiased view of adult mammary gland development and extend to the nonimprinted transcriptome, offering new insights into nutrient transfer between mother and offspring.”
The research was conducted on 80 reciprocal hybrid mice, meaning that the parents were swapped in two combinations to investigate the effects of maternal versus paternal gene contributions. The females were analyzed at 10 time points of mammary gland development. Mammary glands were collected at pregnancy days 5.5, 9.5, and 14.5; lactation days 5, 10, and 15; and involution days 1, 6, and 14. These nine time points, together with a control sample from virgin mice collected during the estrus phase (the phase of the mouse reproductive cycle that serves as a baseline for comparing gene changes in the mammary glands during pregnancy and lactation), create a total of 10 time points throughout the developmental cycle of the adult mammary gland. The lab work involved removing mammary glands, isolating and labeling cells, and storing RNA at -80°C… The researchers tracked which genes were active at different stages of development.
Why were these ten different time points chosen?
Dr Geula Hanin, a researcher in the University of Cambridge’s Department of Genetics and the first author of the report, said: “We chose these ten time points because the breast is an incredibly dynamic organ: it goes through dramatic changes depending on whether a woman is pregnant, breastfeeding, or has just weaned her child. We wanted to capture that full story. During pregnancy, the breast is busy constructing the structures needed to make milk, and the changes in early, mid, and late pregnancy are strikingly different. Once breastfeeding begins, we focused on three key stages: first, the production of colostrum – the earliest milk, packed with immune protection for the newborn; then the peak of lactation, when milk output is at its highest; and finally the later phase, when the baby is starting to eat solid foods and the milk gradually adapts to complement this new diet.
Finally, we examined what happens after weaning, during a process called involution. At first, the milk is still present in the gland, but then the breast begins clearing out milk and returning the tissue to its resting state. This process is fascinating but also important because when it doesn’t go smoothly, it can sometimes contribute to the development of breast cancer. By looking across all these stages, we can really see how the breast builds, functions, and then remodels itself – and how those changes might influence health.”
Does it matter in this case whether the pregnancy is the first or the second?
Dr. Hanin: This is a really important point. A first pregnancy is quite different from later ones, because the breast is essentially “learning on the job.” By the second pregnancy, the tissue has already been through the process once, so many of the changes happen more quickly and efficiently. In this study, we focused specifically on the first pregnancy to capture that initial transformation as the breast learns how to make and deliver milk.
The study’s findings
The results showed that genes linked to breastfeeding difficulties, such as insufficient milk supply, are active not only in breast cells that produce milk, but also in other cells that help with milk release. This suggests that the challenge may not lie in milk production itself, but in the delicate mechanism of its release. The researchers also found that genes linked to breast cancer become active in multiple cell types after breastfeeding ends. Also…”The analysis identified 25 imprinted genes monoallelically expressed in the mammary gland, with several showing allele-specific expression in distinct cell types,” as noted in the study. In other words, imprinted genes are genes whose activity differs depending on whether they are inherited from the mother or the father; in this case, they detected 25 such genes that are activated at specific stages of mammary gland development.
Looking ahead 5–10 years
Let’s say 5–10 years from now: how important could this be for future mothers, and what is your next goal?
Dr. Hanin: Looking 5–10 years ahead, I think this work could make a real difference for mothers and babies. Breastfeeding is so important for both infant and maternal health, yet it often fails for reasons we still don’t fully understand. By identifying the specific cells and genes involved in those problems, we’ve opened the door to new ways of supporting women when things don’t go smoothly. Another important aspect is postpartum breast cancer, which is both aggressive and frequently underdiagnosed. Our findings reveal some of the earliest molecular signals in the breast after weaning, which could one day help with earlier detection or even prevention of this form of cancer.
On a broader level, our study shows not only how milk-producing cells work, but also how other cell types in the breast, like fat, connective tissue, and blood vessel cells, play important roles in both lactation and disease. We’ve also mapped how maternal and paternal genes come into play, which adds a fascinating evolutionary angle alongside the clinical implications. Finally, we’ve made all of our data publicly available, so that other researchers around the world can build on it – whether they’re studying breastfeeding, breast cancer, or even wider questions in genetics and development. Our next goal is to take these insights further, to translate them into practical advances that can directly support mothers and their children.
According to UNICEF, global rates of exclusive breastfeeding during the first six months of life have increased by 10 percentage points over the past decade, reaching 48% in 2023, close to the World Health Assembly target of 50% by 2025. However, many women still face challenges with breastfeeding, and the potential risk of breast cancer can develop in young women within 5 to 10 years after giving birth. This underscores the importance of the study’s results, offering valuable insights for women’s health and developing effective strategies to support breastfeeding and prevent disease.
Image: UNICEF breastfeeding
