ReviewMammary gland: From embryogenesis to adult life
Introduction
In mammals, including humans, the mammary gland has a development that begins during prenatal life, but it also consists of several stages during postnatal life (neonatal, puberty up to pregnancy) (Richert et al., 2000, Castrogiovanni et al., 2014, Musumeci et al., 2013). The mammary glands are modified and highly specialized sweat glands. The whole system of mammary ducts is included in the context of an adipose mesenchyme that exerts considerable influence on its growth and evolution (Giordano et al., 2014). These influences are the result of a complex multifactorial process that progresses through both prenatal and postnatal stages (Richert et al., 2000, Musumeci et al., 2014, Musumeci et al., 2015). The histogenesis of the mammary gland begins early in the embryonic period with the development, in females, of a draft consisting of a small-branched channels system located in the mammary adipose tissue. Although its development proceeds with the isometric growth until the neonatal period, a greater impulse is in the prepubertal period; it continues in the peripubertal phase with elongation and branching of the ducts; finally, it culminates in the pubertal stage characterized by full sexual maturity, period in which the branching of the ducts increases and on their tips, the alveolar buds will form. Pregnancy represents the last developmental stage of the mammary gland during which the functional differentiation of the glandular parenchyma takes place in order to prepare the lobule–alveolar structure to lactation (Richert et al., 2000). This structure undergoes involution in response to the interruption of pregnancy and the cessation of menstrual cycles (Fig. 1).
The regulation of all the stages of mammary gland development, characterized by repeated cycles of morphological growth and functional differentiation, is given by a series of systemic endocrine signals (Neville et al., 2002, Need et al., 2014, Musumeci et al., 2014, Musumeci et al., 2015). Nevertheless, it seems also necessary to consider the existence of other regulatory molecules capable of integrating all the involved signals, both the endocrine ones and those originating from the surrounding microenvironment (mesenchymal cells, cellular matrix, growth factors, hormones, paracrine/autocrine factors, cytokines, etc.). Only the integration and coordination of all these factors ensures the optimal development of the mammary gland, the maintenance of its own evolutionary destiny and tissue identity.
The coordination of this complex process is largely organized and supported by the Homeobox genes (Chen and Sukumar, 2003, Satoh et al., 2004, Pagani et al., 2010). However, even if the spatiotemporal regulation of the proliferative, differentiative and functional cycles of the mammary gland by the homeotic genes may be effective, it is always possible that their wrong expression in mammary cells may lead to a defective or insufficient cell differentiation or, on the contrary, to an uncontrolled proliferation, contributing to the onset of a neoplastic process (Ligresti et al., 2008, Douglas and Papaioannou, 2013, Howard and Lu, 2014).
Section snippets
Embryogenesis of the human mammary gland
In humans, as well as in other mammals, the tegumentary ectodermal epithelium, after the interaction with the mesenchymal cells of the underlying dermis, originates the epidermis and activates the differentiation of various specialized dermal–epidermal structures such as hair, nails, teeth and several exocrine glands such as sebaceous, sweat and mammary glands. These latter arise, since the end of week 4 of embryonic development, from bilateral thickenings that extend from the axillary to the
Conclusion
We can conclude that transcription factors play an essential role in development of the mammary gland, though we should emphasize that most of them are also widely expressed in different extra-mammary tissues. The specific function of these regulatory proteins in the morphogenesis of the mammary gland is their ability to interact with other cellular cofactors, which are also proteins. Several recent studies indicate that many of these transcription factors are important in determining the
Acknowledgements
This study was supported by grants provided by FIR 2014-2016, University of Catania, Italy. The authors would like to thank Prof. Iain Halliday for commenting and making corrections to the paper.
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