Multiscale imaging of basal cell dynamics in the functionally mature mammary gland

Abstract

The mammary epithelium is indispensable for the continued survival of more than 5,000 mammalian species. For some, the volume of milk ejected in a single day exceeds their entire blood volume. Here, we unveil the spatiotemporal properties of physiological signals that orchestrate the ejection of milk from alveolar units and its passage along the mammary ductal network. Using quantitative, multidimensional imaging of mammary cell ensembles from GCaMP6 transgenic mice, we reveal how stimulus evoked Ca2+ oscillations couple to contractions in basal epithelial cells. Moreover, we show that Ca2+-dependent contractions generate the requisite force to physically deform the innermost layer of luminal cells, compelling them to discharge the fluid that they produced and housed. Through the collective action of thousands of these biological positive-displacement pumps, each linked to a contractile ductal network, milk begins its passage toward the dependent neonate, seconds after the command.

Development and Pathology of the Equine Mammary Gland

“…When a mother suckles her offspring, the maternally derived neuropeptide oxytocin binds to its cognate receptor expressed on mammary basal (myoepithelial) cells stimulating intracellular calcium signalling that results in contraction of the myoepithelial cells and milk expulsion [45]. This process is known as 'milk let down'.…”

Animal Models for In Vivo Lactation Studies: Anatomy, Physiology and Milk Compositions in the Most Used Non-Clinical Species: A Contribution from the ConcePTION Project

“…40% drop). Thereafter, it continues to decrease but in a less pronounced manner and increases in the last days of lactation (days [25][26][27][28]. The decreasing pattern was also found in humans, although the percentage decrease is not that high.…”

“…From a histological point of view, mammary glands can indeed be generally described as an epithelial bilayer, within adipose tissue, with two key cell populations: luminal cuboidal cells and star-shaped myoepithelial cells [ 26 , 27 ]. The first population lines the lactiferous ducts, form the inner portion, while myoepithelial cells constitute the outer portion of the bilayer and are responsible for milk ejection [ 28 ].…”

“…Suckling or manual stimulation of the teat is locally detected, and the stimulus is transmitted by sensory afferents to the hypothalamus, which then initiates oxytocin release from the neurohypophysis. This hormone stimulates the myoepithelial cells that surround the alveoli to contract and cause milk to flow from the alveoli through the duct system to the teat end [ 28 , 46 ]. The physiology of lactation does not differ drastically amongst species, but the duration and the yield of both colostrum and milk are highly variable ( Table 2 ).…”

Developing mammary terminal duct lobular units have a dynamic mucosal and stromal immune microenvironment

“…There has been a relative paucity of focus on myoepithelial proliferation within the developing breast or mammary gland prior to pregnancy. During lactation, myoepithelial cells contract to deform alveoli, facilitating milk release in response to oxytocin stimulation (Stevenson et al, 2020). Our identification of proliferation within the myoepithelial compartment pre-pregnancy suggests that studying basal epithelial replication during this period may provide new insights into udder development relevant to lactation efficiency.…”