**1. Introduction**

The origin of the mammary gland in the fossil record appeared about 220–300 million years ago in the Carboniferous geological period and was evolving for 130 million years to its current mammalian form [1]. In its earliest evolutionary form, the glandular structure ancestral to the mammary gland had functioned as a source of secretion that helped eggs withstand desiccation associated with incubation on land and appeared among tetrapods or among the

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

basal amniotes-vertebrates. Comparison of mammary-expressed genes between mammalian taxa revealed the sheared presence and high degree of conservation of the genes. Mammary gland fully developed prior to emergence of diverse groups of mammals, and the milk compounds (fat globules, whey proteins, casein micelles, and sugars) are structurally similar across all mammalian species [2].

After birth, in the postnatal life until puberty, the gland remains quiescent and exhibits only minimal ductal growth. Interspecies differences occur in the extent of mammary gland development that occurs in neonates. In mice, the mammary tree consists of long, infrequently branching ducts and TEBs. Human mammary gland has a more complex structure composed of approximately 15–20 lobes of glandular tissue, each containing a lactiferous duct that opens onto the breast surface through the mammary pit [9]. In the case of ruminants, the mammary gland consists of terminal ductal units (TDU), which are formed during prenatal development accomplished through the coordinated growth, branching and extension of TDU, as well as growth of the loose connective tissue that surrounds the TDU as it invades the mammary fat pad [8].

Stromal-Epithelial Interactions during Mammary Gland Development

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With the onset of puberty, a combination of systemic and paracrine hormones induces TEBs to reappear at the ductal tips accompanied by a significant increase in the growth rate. Elongation and branching of the ducts, regulated by proliferation and migration of TEBs cells, rely on both endocrine and local growth regulatory signals, extracellular matrix (ECM) remodeling, and stromal influence. With the beginning of puberty, the epithelium bifurcates and invades into the surrounding stroma creating a tree-like structure of mammary ducts. The majority of mammary ductal morphogenesis occurs with onset of ovarian function because of the cyclic influence of reproductive hormones. Further, with each estrus cycle, the alveoli and ducts undergo cyclic expansion and maturation, followed by a modest regression phase as ovarian hormone levels rise and fall, respectively. These events are under the control of a complex interplay of circulating essential steroids (estrogen and progesterone), polypeptide systemic hormones (e.g., prolactin), metabolic hormones that are responsible for coordinating the body's response to metabolic homeostasis (e.g., growth hormone—GH, glucocorticoids, insulin, leptin), as well as locally acting paracrine hormones and growth factors (e.g., insulin-like growth factor I— IGF-I, hepatocyte growth hormone—HGF, transforming growth factor-β—TGF-β, epidermal growth factor—EGF) [10]. It is worth noting that the hormone acting network regulating the

development of the mammary epithelium varies between different species.

reduction of lobuloalveolar structures.

**3. Structure of fully developed mammary gland**

The mammary gland is able to undergo its terminal differentiation only in female mammals during pregnancy and lactation. With the onset of gestation period and increased levels of progesterone, alveolar structures give rise to lobuloalveolar structures capable of milk production during lactation. After weaning of the offspring (or termination of milking), the gland undergoes post-lactating regression referred as involution, with loss of most of epithelial components gained during the preceding event. Early involution is evidenced by apoptotic death of alveolar secretory epithelial cells which subsequently are removed by efferocytosis (the process of engulfing and destroying apoptotic cells) [11]. Second phase of the mammary gland involution is defined by degradation of basement membrane and ECM proteins and

Fully developed mammary gland is created by two compartments: epithelial and stromal. The epithelial compartment, termed parenchyma, is composed of the branching network of ducts

In contrast to most organs that achieve morphological maturity during prenatal development in the process defined as morphogenesis, the majority of mammary gland development leading to its complex morphological maturity occurs mostly during postnatal life of mammals [3]. During embryogenesis, the mammary gland development is driven mostly by mesenchymal cells. In postnatal life, subsequent stages of glandular development: mammogenesis (development of mammary epithelial tissue), lactogenesis (functional differentiation of the mammary epithelium leading to initiation of milk secretion), galactopoiesis (maintenance of milk secretion), and involution (regression of the glandular epithelium), take place under significant regulation of hormones. In parallel, the intraglandular milieu plays also an important role in controlling the progress of events related to mammary gland morphogenesis.
