Mammary gland development

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Mammary gland development is characterized by the unique process by which the epithelium invades the stroma. The development of the mammary gland occurs mainly after birth. During puberty, tubule formation is coupled with branching morphogenesis which establishes the basic arboreal network of ducts emanating from the nipple.[1]

Developmentally, mammary gland epithelium is constantly produced and maintained by rare epithelial cells, dubbed as mammary progenitors which are ultimately thought to be derived from tissue-resident stem cells.[citation needed]

Embryonic mammary gland development[edit]

Embryonic mammary gland development can be divided into a series of specific stages. Initially, the formation of the milk lines that run between the fore and hind limbs bilaterally on each side of the midline occurs around embryonic day 10.5 (E10.5). The second stage occurs at E11.5 when placode formation begins along the mammary milk line. This will eventually give rise to the nipple. Lastly, the third stage occurs at E12.5 and involves the invagination of cells within the placode into the mesenchyme, leading to a mammary anlage (biology).[2]

The primitive (stem) cells are detected in embryo and their numbers increase steadily during development [3]

Pre-pubertal mammary gland development[edit]

Postnatally, the mammary ducts elongate into the mammary fat pad. Then, starting around four weeks of age, mammary ductal growth increases significantly with the ducts invading towards the lymph node. Terminal end buds, the highly proliferative structures found at the tips of the invading ducts, expand and increase greatly during this stage. This developmental period is characterized by the emergence of the terminal end buds and lasts until an age of about 7–8 weeks.

Pubertal mammary gland[edit]

By the pubertal stage, the mammary ducts have invaded to the end of the mammary fat pad. At this point, the terminal end buds become less proliferative and decrease in size. Side branches form from the primary ducts and begin to fill the mammary fat pad. Ductal development decreases with the arrival of sexual maturity and undergoes estrous cycles (proestrus, estrus, metestrus, and diestrus). As a result of estrous cycling, the mammary gland undergoes dynamic changes where cells proliferate and then regress in an ordered fashion.[4]


Pregnancy[edit]

During pregnancy, the ductal systems undergo rapid proliferation and form alveolar structures within the branches to be used for milk production.

Lactation[edit]

After delivery, lactation occurs within the mammary gland; lactation involves the secretion of milk by the luminal cells in the alveoli. Contraction of the myoepithelial cells surrounding the alveoli will cause the milk to be ejected through the ducts and into the nipple for the suckling pups.

Involution[edit]

Upon weaning of the pups, lactation stops and the mammary gland turns in on itself (involution). This process involves the controlled collapse of mammary epithelial cells where cells begin apoptosis in a controlled manner, reverting the mammary gland back to a pubertal state.

Estrogen receptors[edit]

Development is caused by activation of estrogen receptor alpha, progesterone receptors, and prolactin receptors contained in mammary cells.[5] Estradiol, progesterone, and prolactin normally activate the respective receptors that cause breast growth throughout stages of development.[5] Some phytoestrogens, such as 8-prenylnaringenin, may activate these estrogen receptors to stimulate mammary gland development.[6] Estrogen receptor expression in the mammary gland is controlled by the GATA-3 transcription factor [7][8]

References[edit]

  1. ^ Sekhri, KK (Sep 1967). "Studies of mouse mammary glands. I. Cytomorphology of the normal mammary gland". J Natl Cancer Inst. 39 (3): 459–90. PMID 6053715.  |first2= missing |last2= in Authors list (help); |first3= missing |last3= in Authors list (help)
  2. ^ Hens, JR; Wysolmerski JJ (10 Aug 2005). "Key stages of mammary gland development: molecular mechanisms involved in the formation of the embryonic mammary gland". Breast Cancer Res. 7 (5): 220–4. doi:10.1186/bcr1306. PMC 1242158. PMID 16168142. 
  3. ^ Makarem, M; Eaves C (Apr 2013). "Stem Cells and the Developing Mammary Gland". J Mammary Gland Biol Neoplasia. 18 (2): 209–19. doi:10.1007/s10911-013-9284-6. PMID 23624881. 
  4. ^ Daniel, CW; Smith, GH (January 1999). "The mammary gland: a model for development". Journal of Mammary Gland Biology and Neoplasia 4 (1): 3–8. doi:10.1023/A:1018796301609. PMID 10219902. 
  5. ^ a b Brisken; Malley (December 2, 2010). "Hormone Action in the Mammary Gland". Cold Spring Harbor Perspectives in Biology (Cold Spring Harb Perspect Biol) 2 (12): a003178. doi:10.1101/cshperspect.a003178. PMC 2982168. PMID 20739412 
  6. ^ Overk, CR; Guo, J; Chadwick, LR; Lantvit, DD; Minassi, A; Appendino, G; Chen, SN; Lankin, DC; Farnsworth, NR; Pauli, GF; Van Breemen, RB; Bolton, JL (2008). "In vivo estrogenic comparisons of Trifolium pratense (red clover) Humulus lupulus (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin.|". Chemico-biological interactions 176 (1): 30–39. doi:10.1016/j.cbi.2008.06.005. PMC 2574795. PMID 18619951 
  7. ^ Asselin-Labat, ML; Sutherland, KD; Barker, H; Thomas, R; Shackleton, M; Forrest, NC; Hartley, L; Robb, L; Grosveld, FG; van der Wees, J; Lindeman, GJ; Visvader, JE (Feb 2007). "Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation.". Nature Cell Biology 9 (2): 201–9. doi:10.1038/ncb1530. PMID 17187062. 
  8. ^ Kouros-Mehr, Hosein; Slorach, EM; Sternlicht, MD; Werb, Z (Dec 1, 2006). "GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland.". Cell 127 (5): 1041–55. doi:10.1016/j.cell.2006.09.048. PMC 2646406. PMID 17129787.