Integumentary System - Mammary Gland Development
The mammary gland is the functional structure of the female breast and develops initially as a skin specialization. Breast growth and appearance in male and female children are virtually identical prior to puberty.
At puberty females, under the influence of mainly sex hormone signaling, undergo a series of growth changes that can be defined by a series of "Tanner Stages".
In pregnancy, an additional series of signals leads to further changes in breast structure. The key function of this process is to prepare the maternal breast for lactation and providing nutrition through milk to the newborn. (More? Normal Development - Milk)
At menopause, changes in sex hormone secretion can once again alter breast structure.
The breast also associated with oncogenesis (breast cancer). Research in this area has been aided by the discovery in 1994 of the two breast cancer susceptibility genes (BRCA1, BRCA2). There is some developing evidence that modification of stem cells (progenitor cells) that exist in the mammary gland may also contribute to neoplasms (cancer).
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Some Recent Findings
- Human Embryology (2nd ed.) Larson Chapter 14 p443-455
- The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Chapter 20: P513-529
- Before We Are Born (5th ed.) Moore and Persaud Chapter 21: P481-496
- Essentials of Human Embryology Larson Chapter 14: P303-315
- Human Embryology, Fitzgerald and Fitzgerald
- Color Atlas of Clinical Embryology Moore Persaud and Shiota Chapter 15: p231-236
- week 6 epidermis downgrowth into dermis, modified sweat glands
- epithelia/mesenchyme inductive interaction, mesenchyme forms connective tissue and fat
- mammary ridges - mammary bud formation, pair of ventral regions axilla to inguinal
- pectoral regions generate breasts
- buds branch to form lactiferous ducts, only main duct formed at birth
- mammary pit - forms fetal period
- areola - depressed region at gland, proliferation of connective tissue postnatally
- prior to puberty male and female glands the same
- sex hormone estrogen stimulate growth, full development approx 20 years
- growth also influenced by other hormones - progereterone, prolactin, corticoids, growth hormone
- mainly fat and connective tissue deposition
Tanner Mammary Development Stages
In 1976 Tanner and Whitehouse established a series of descriptive stages for primary and secondary sexual characteristic development at puberty. The female secondary sex characteristics of breast development were divided into five numbered (1 - 5) "Tanner Stages".
Mammary Glands Pregnancy
During pregnancy raised estrogens and progesterone stimulate gland development, secretory alveolar structures form and differentiate, leading to milk production in late pregnancy and milk secretion during lactation. Breasts are hemispherical in shape due to fat deposition. After birth, neonatal lactation supports further growth/development.
Mammary Glands Weaning
After the infant ceases breast feeding, weaning, the mammary gland milk-producing epithelial cells undergo a process called "involution", that requires cell apoptosis.
E10 - milk line first formed by a slight thickening and stratification of the surface ectoderm.
E11.5 - the milk line breaks up into individual placodes and the underlying mammary mesenchyme begins to condense.
E15.5 - mammary epithelium begins to proliferate at the tip and the primary sprout pushes through the mammary mesenchyme towards the underlying fat pad.
E18.5 - elongating duct has now grown into the fat pad and has branched into a small ductal system. Cells of the mammary mesenchyme have formed the nipple, which is made of specialized epidermal cells.
Timeline data from review
Canonical Wnt signals are transduced through a Frizzled receptor and the LRP5 or LRP6 co-receptor. Loss of Lrp6 compromises Wnt/beta-catenin signaling and interferes with mammary placode, fat pad, and branching development during embryogenesis.
- Links: Mouse Timeline Detailed
Abnormalities occur in approximately 1% of female population and include in both sexes:
- polymastia - extra breast
- polytheli - extra nipple
- supernumerary nipple (relatively common in males)
- gynecomastia (Greek, gyne = woman, mastos = breast) is the excessive development of the male breast, which can occur transiently in puberty or due to other (hormonal) abnormalities.
International Classification of Diseases
Q83 Congenital malformations of breast
Excl.: absence of pectoral muscle (Q79.8)
- Q83.0 Congenital absence of breast with absent nipple
- Q83.1 Accessory breast Supernumerary breast
- Q83.2 Absent nipple
- Q83.3 Accessory nipple Supernumerary nipple
- Q83.8 Other congenital malformations of breast Hypoplasia of breast
- Q83.9 Congenital malformation of breast, unspecified
In 1994, two breast cancer susceptibility genes were identified BRCA1 on chromosome 17 and BRCA2 on chromosome 13.
When an individual carries a mutation in either BRCA1 or BRCA2, they are at an increased risk of being diagnosed with breast or ovarian cancer at some point in their lives. Normal function of these genes was to participate in repairing radiation-induced breaks in double-stranded DNA. It is though that mutations in BRCA1 or BRCA2 might disable this mechanism, leading to more errors in DNA replication and ultimately to cancerous growth. (text modified from: NCBI genes and disease)
- ↑ Krista Yorita Christensen, Mildred Maisonet, Carol Rubin, W Dana Flanders, Carolyn Drews-Botsch, Celia Dominguez, Michael A McGeehin, Michele Marcus Characterization of the correlation between ages at entry into breast and pubic hair development. Ann Epidemiol: 2010, 20(5);405-8 PMID:20382343
- ↑ Dara Cannata, Danielle Lann, Yingjie Wu, Sebastien Elis, Hui Sun, Shoshana Yakar, Deborah A Lazzarino, Teresa L Wood, Derek Leroith Elevated circulating IGF-I promotes mammary gland development and proliferation. Endocrinology: 2010, 151(12);5751-61 PMID:20926579
- ↑ Pepper Schedin, Russell C Hovey Editorial: The mammary stroma in normal development and function. J Mammary Gland Biol Neoplasia: 2010, 15(3);275-7 PMID:20824491
- ↑ J M Tanner, R H Whitehouse Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch. Dis. Child.: 1976, 51(3);170-9 PMID:952550
- ↑ Christine J Watson Involution: apoptosis and tissue remodelling that convert the mammary gland from milk factory to a quiescent organ. Breast Cancer Res.: 2006, 8(2);203 PMID:16677411 | [http://breast-cancer-research.com/content/8/2/203 Breast Cancer Res.
- ↑ Beatrice Howard, Alan Ashworth Signalling pathways implicated in early mammary gland morphogenesis and breast cancer. PLoS Genet.: 2006, 2(8);e112 PMID:16933995 | PLoS Genet.
- ↑ Gertraud W Robinson Cooperation of signalling pathways in embryonic mammary gland development. Nat. Rev. Genet.: 2007, 8(12);963-72 PMID:18007652
- ↑ Charlotta Lindvall, Cassandra R Zylstra, Nicole Evans, Richard A West, Karl Dykema, Kyle A Furge, Bart O Williams The Wnt co-receptor Lrp6 is required for normal mouse mammary gland development. PLoS ONE: 2009, 4(6);e5813 PMID:19503830
Christophe M Lefèvre, Julie A Sharp, Kevin R Nicholas Evolution of lactation: ancient origin and extreme adaptations of the lactation system. Annu Rev Genomics Hum Genet: 2010, 11();219-38 PMID:20565255
Pamela Cowin, John Wysolmerski Molecular mechanisms guiding embryonic mammary gland development. Cold Spring Harb Perspect Biol: 2010, 2(6);a003251 PMID:20484386
Constantine Dimitrakakis, Carolyn Bondy Androgens and the breast. Breast Cancer Res.: 2009, 11(5);212 PMID:19889198
Anne M Rowzee, Deborah A Lazzarino, Lauren Rota, Zhaoyu Sun, Teresa L Wood IGF ligand and receptor regulation of mammary development. J Mammary Gland Biol Neoplasia: 2008, 13(4);361-70 PMID:19020961
Heather L LaMarca, Jeffrey M Rosen Minireview: hormones and mammary cell fate--what will I become when I grow up? Endocrinology: 2008, 149(9);4317-21 PMID:18556345
Radhika Nair, Simon Junankar, Sandra O'Toole, Jaynish Shah, Alexander D Borowsky, J Michael Bishop, Alexander Swarbrick Redefining the expression and function of the inhibitor of differentiation 1 in mammary gland development. PLoS ONE: 2010, 5(8);e11947 PMID:20689821
Thomas W Owens, Fiona M Foster, Jolanta Tanianis-Hughes, Julia Y Cheung, Lisa Brackenbury, Charles H Streuli Analysis of inhibitor of apoptosis protein family expression during mammary gland development. BMC Dev. Biol.: 2010, 10();71 PMID:20584313
Nicholas McCormick, Vanessa Velasquez, Lydia Finney, Stefan Vogt, Shannon L Kelleher X-ray fluorescence microscopy reveals accumulation and secretion of discrete intracellular zinc pools in the lactating mouse mammary gland. PLoS ONE: 2010, 5(6);e11078 PMID:20552032 | PLoS One. Holly E Barker, Gordon K Smyth, James Wettenhall, Teresa A Ward, Mary L Bath, Geoffrey J Lindeman, Jane E Visvader Deaf-1 regulates epithelial cell proliferation and side-branching in the mammary gland. BMC Dev. Biol.: 2008, 8();94 PMID:18826651
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