Parity reduces mammary repopulating activity but does not affect mammary stem cells defined as CD24 + CD29/CD49fhi in mice

Genevieve V. Dall, Jessica Vieusseux, Yashar Seyed-Razavi, Nathan Godde, Mandy Ludford-Menting, Sarah M. Russell, Alan Ashworth, Robin L. Anderson, Gail P. Risbridger, Mark Shackleton, Kara L. Britt

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3 Citations (Scopus)


Background: Breast cancer (BCa) mortality is decreasing with early detection and improvement in therapies. The incidence of BCa, however, continues to increase, particularly estrogen-receptor-positive (ER +) subtypes. One of the greatest modifiers of ER + BCa risk is childbearing (parity), with BCa risk halved in young multiparous mothers. Despite convincing epidemiological data, the biology that underpins this protection remains unclear. Parity-induced protection has been postulated to be due to a decrease in mammary stem cells (MaSCs); however, reports to date have provided conflicting data. Methods: We have completed rigorous functional testing of repopulating activity in parous mice using unfractionated and MaSC (CD24midCD49fhi)-enriched populations. We also developed a novel serial transplant method to enable us to assess self-renewal of MaSC following pregnancy. Lastly, as each pregnancy confers additional BCa protection, we subjected mice to multiple rounds of pregnancy to assess whether additional pregnancies impact MaSC activity. Results: Here, we report that while repopulating activity in the mammary gland is reduced by parity in the unfractionated gland, it is not due to a loss in the classically defined MaSC (CD24+CD49fhi) numbers or function. Self-renewal was unaffected by parity and additional rounds of pregnancy also did not lead to a decrease in MaSC activity. Conclusions: Our data show instead that parity impacts on the stem-like activity of cells outside the MaSC population.

Original languageEnglish
Pages (from-to)565-575
Number of pages11
JournalBreast Cancer Research and Treatment
Issue number3
Publication statusPublished - Oct 2020


  • Breast cancer
  • Mammary fat pad transplants
  • Parity
  • Stem cells

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