Pubertal Mammary Gland Development: Elucidation of In Vivo Morphogenesis Using Murine Models

Abstract

During the past 25 years, the combination of increasingly sophisticated gene targeting technology with transplantation techniques has allowed researchers to address a wide array of questions about postnatal mammary gland development. These in turn have significantly contributed to our knowledge of other branched epithelial structures. This review chapter highlights a selection of the mouse models exhibiting a pubertal mammary gland phenotype with a focus on how they have contributed to our overall understanding of in vivo mammary morphogenesis. We discuss mouse models that have enabled us to assign functions to particular genes and proteins and, more importantly, have determined when and where these factors are required for completion of ductal outgrowth and branch patterning. The reason for the success of the mouse mammary gland model is undoubtedly the suitability of the postnatal mammary gland to experimental manipulation. The gland itself is very amenable to investigation and the combination of genetic modification with accessibility to the tissue has allowed an impressive number of studies to inform biology. Excision of the rudimentary epithelial structure postnatally allows genetically modified tissue to be readily transplanted into wild type stroma or vice versa, and has thus defined the contribution of each compartment to particular phenotypes. Similarly, whole gland transplantation has been used to definitively discern local effects from indirect systemic effects of various growth factors and hormones. While appreciative of the power of these tools and techniques, we are also cognizant of some of their limitations, and we discuss some shortcomings and future strategies that can overcome them.

Induction of phenotypic changes in HER2-postive breast cancer cells in vivo and in vitro

“…The mammary gland is an excellent system to study stem cells, microenvironments, and development as the vast majority of cellular growth and differentiation occurs during puberty [7]. The glandular epithelium undergoes vast proliferation and differentiation during puberty.…”

Molecular signature of the putative stem/progenitor cells committed to the development of the bovine mammary gland at puberty

“…Many studies have reported that mammary development at puberty is triggered by the main steroid hormones estradiol and progesterone (for review see 2 ). Indeed, experiments with PR -deficient mice demonstrated that, at puberty, progesterone is not essential for ductal elongation but is critical in inducing side-branching 24 .…”

“…At the end of its development, the mammary epithelium has the appearance of an elaborate tree of ducts and alveoli. After parturition, the alveolar epithelium starts to be fully functional, with mammary epithelial cells secreting milk proteins into the lumen of the alveoli for lactation 2 .…”

Mifepristone Treatment in Pregnant Murine Model Induced Mammary Gland Dysplasia and Postpartum Hypogalactia

“…The reproductive and metabolic hormones, such as estrogen, progesterone (P 4 ), placental lactogen, prolactin (PRL), OT, growth hormone (GH), glucocorticoids, thyroid hormone and insulin, well coordinate and dominate mammary gland development including ductal branching, alveolar bud development and secretion during pregnancy or lactation (Neville et al, 2002;Macias and Hinck, 2012;McNally and Stein, 2017). Estrogen and GH primarily regulate ductal morphogenesis by binding to their receptors during puberty and pregnancy in mice (Kleinberg et al, 2000;McBryan and Howlin, 2017). A balance between P 4 and PRL controls alveolar morphogenesis during pregnancy in mice (Neville et al, 2002;Leehy et al, 2018), while PRL, GH, glucocorticoids, thyroid hormone, and insulin govern milk secretion in mice or rats (Vonderhaar and Ziska, 1989;Flint and Gardner, 1994;Menzies et al, 2010).…”