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TISSUE-SPECIFIC STEM CELLS

Evidence That an Early Pregnancy Causes a Persistent Decrease in the Number of Functional Mammary Epithelial Stem Cells—Implications for Pregnancy-Induced Protection Against Breast Cancer

^aThe Lester and Sue Smith Breast Center,
^bDivision of Biostatistics, Dan L. Duncan Cancer Center, and
^cDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, Texas, USA

Key Words. Epithelial cells • Mammary glands • Pregnancy • Stem cells • Stem cell transplantation

Correspondence: Correspondence: Yi Li, Ph.D., One Baylor Plaza BCM 600, Houston, Texas 77030, USA. Telephone: 713-798-3963; Fax: 713-798-1659; e-mail: liyi{at}bcm.edu

Received on February 4, 2008; accepted for publication on September 3, 2008.

First published online in STEM CELLS EXPRESS  September 11, 2008.

A completed pregnancy at a young age reduces a woman's lifetime risk of breast cancer by up to 50%. A similar protective effect of an early pregnancy has been observed in rodent models using chemical carcinogens. However, the mechanisms responsible for this protective effect remain unclear. Stem cells have been proposed to be the cells of origin for breast cancer. We hypothesized that an early pregnancy reduces adult levels of either mammary stem cells or mammary multipotent progenitor cells. Unsorted mammary cells from adult mice that had undergone an early parity had the same mammosphere formation efficiency as cells from age-matched virgin mice. However, when we transplanted adult mammary cells in limiting dilutions into cleared fat pads of syngeneic mice, we found a significant reduction in the outgrowth potential of the cells from early parous mice compared with age-matched virgin mice. The extent of fat pad filling in successful outgrowths did not change, suggesting that although mammary stem cells in parous mice retained their functional competence, the number of mammary stem cells was reduced. Our results provide the first direct evidence that an early pregnancy has an effect on mammary stem cells.

Disclosure of potential conflicts of interest is found at the end of this article.