Study of breast cell changes in motherhood provides clues to breastfeeding difficulties

(Press-News.org) In a study in mice, researchers have identified genes associated with the dramatic transformation of the mammary gland in pregnancy, breastfeeding, and after breastfeeding as it returns to its resting state.

Their results form the most detailed atlas of genetic expression ever produced for the adult developmental cycle of the mammary gland. They are published today in the journal Nucleic Acids Research.

The mammary gland is made up of different cell types, each with a different function - such as fat cells that provide structural support, and basal cells that are crucial for milk ejection.

The team analysed the cellular composition of the mammary gland at ten different time-points from before the first pregnancy, during pregnancy, during breastfeeding, and during a process called involution when the breast tissue is remodelled to its resting state. The mix of cell types changes dramatically through this cycle.

By measuring gene expression in the mammary gland over the same time-points, the researchers were able to link specific genes to their functions at different stages of the developmental cycle.

“Our atlas is the most detailed to date, allowing us to see which genes are expressed in which cell types at each stage of the adult mammary gland cycle,” said Dr Geula Hanin, a researcher in the University of Cambridge’s Department of Genetics, first author of the report. 

The team found that genes associated with breastfeeding disorders such as insufficient milk supply are active not only in the breast cells that produce milk, but also in other cells such as basal cells - which squeeze out the milk as the infant is suckling. This suggests that in some instances, a mechanical problem - rather than a milk production problem - could be the cause and provides a new cell target for investigation.

The study also found that genes associated with postpartum breast cancer become active immediately after weaning in various cell types - including in fat cells, which have previously been overlooked as contributors to breast cancer linked to childbirth. This offers a future potential target for early detection or prevention strategies.

Hanin said: “We’ve found that genes associated with problems in milk production, often experienced by breastfeeding mothers, are acting in breast cells that weren’t previously considered relevant for milk production. We’ve found genes associated with postpartum breast cancer acting in cells that have been similarly overlooked.

“This work provides many potential new ways of transforming maternal and infant health, by using genetic information to both predict problems with breastfeeding and breast cancer, and to tackle them further down the line.”

Breastfeeding affects lifelong health, for example breast-fed babies are less likely to become obese and diabetic. Yet one in twenty women have breastfeeding difficulties, and despite its importance this is a greatly understudied area of women’s health.

Postpartum breast cancer occurs within five to ten years of giving birth and is linked to hormonal fluctuations, natural tissue remodelling, and the changing environment of the mammary gland during involution that makes it more susceptible to malignancy.

The researchers also focused on ‘imprinted genes’- that is, genes that are switched on or off depending on whether they are inherited from the mother or the father. Imprinted genes in the placenta are known to regulate growth and development of the baby in the womb.

The team identified 25 imprinted genes that are active in the adult mammary gland at precise times during the development cycle. These appear to orchestrate a tightly controlled system for managing milk production and breast tissue changes during motherhood.

Some functions of the genes themselves have been identified in previous studies. This new work provides a detailed understanding of when, and where, the genes become active to cause changes in mammary gland function during its adult development cycle.

“Breastfeeding is a fundamental process that’s common to all mammals; we wouldn’t have survived without it. I hope this work will lead to new ways to support mothers who have issues with breastfeeding, so they have a better chance of succeeding,” said Hanin.

Hanin co-leads the Cambridge Lactation Network and is a member of Cambridge Reproduction.

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