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Development of a model for studying the protective role of pregnancy in breast cancer prevention

In experiments performed in Sprague Dawley rats, which is the gold standard animal model for induction of mammary gland differentiation, pregnancy (which takes 21±3 days in rats) has to be completed in order to prevent carcinogen-induced mammary cancer development. In Sprague-Dawley rats, it has been demonstrated that when their first pregnancy was interrupted 12 days after conception and cancer was induced by 7,12-Dimethylbenz(a)anthracene (DMBA) 21 days later,  the number and weight of the tumors per animal in pregnancy-interrupted rats and age-matched virgin rats were similar. However, rats that completed their pregnancy had a significantly reduced amount of tumors. Completion of the first pregnancy results in significant differentiation of the mammary gland. This differentiation advances even further with milk production and secretion and persists until weaning.  After weaning, , the regression of the lobular structures  occurs, and the remaining cells exhibit acquisition of new features such as proliferative rate reduction and increased  capactity to repair carcinogen-damaged DNA. These new features, which are structural, functional and molecular in nature, persist in the mammary gland, resulting in a significant reduction in cancer incidence. Gene expression analysis identified a genomic signature that clearly distinguishes nulliparous (no offspring) from parous rodents’ gene expression profile and explains the almost total refractoriness of the parous rat mammary gland to develop neoplasm after carcinogen exposure.