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Gillian K Szabo and Laura N Vandenberg

In the past several decades, the incidence of two male breast diseases, gynecomastia and male breast cancer, have increased in human populations. Whereas male breast cancer remains a rare disease, gynecomastia, a condition that arises due to abnormal development and growth of the male breast epithelium, is fairly common. In this review, we present the male mouse mammary gland as a potential model to understand human male breast diseases. Even though the male mouse typically lacks nipples, the male retains a small mammary rudiment with epithelium that is highly sensitive to estrogenic chemicals during the perinatal and peripubertal periods. In just the last few years, our understanding of the biology of the male mouse mammary gland has expanded. Researchers have characterized the complexity and size of the male mammary epithelium across the life course. Studies have documented that the male mouse mammary gland has left-right asymmetric morphologies, as well as asymmetries in the responsiveness of the left and right glands to estrogens. Recent studies have also revealed that the effect of xenoestrogens on the male mammary gland can differ based on the timing of evaluation (prior to puberty, in puberty, and in adulthood) and the administered dose. Based on the available evidence, we argue that there is a strong case that estrogenic chemicals promote the growth of the male mouse epithelium, consistent with human gynecomastia. We also argue that these outcomes should be characterized as adverse effects and should be considered in regulatory decision-making.