The Mammary Gland

Mammary glands are the distinguishing characteristics of all mammals that have evolved to nourish the newborn offspring for a certain period of post-natal life. It is an exocrine gland modified from sweat (sudoriferous) gland.

25.1.1 External Anatomy of Mammary Gland

The development of mammary gland is almost similar in different species but there are striking differences among species in regards to the general anatomy of the mammary gland (Table 25.1).

Mature mammary gland consists of udder, teat or nipple, associated ducts, and alveoli composed of epithelial secretory cells and supporting tissues.

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The largest mammary gland is seen in blue whales. They have two mammary glands like human and each weighted around 250 pounds and 5 ft in length. The glands produce around 37,500 pounds of milk during a single lactation cycle.

Table 25.1 Comparative features of mammary glands in different species

Source: Nickerson and Akers (2011)

25.1.1.1 Udder

In bovines, the udder is composed of four mammary glands. Being a skin gland, the udder is covered with hair except for the teats. The appearance of udder of bovines is square or more or less rounded and saccular. The right and left halves of udder are separated by a longitudinal intermammary groove or sulcus intermammaricus. The separation of the front and rear udder quarters is not well demarcated exter­nally but internally a thin connective tissue provides anatomical barriers between the front and rear glands (quarters) on either side of the udder and there are no direct connections between front and rear udder quarters. Further, the rear quarter produces 60% of total milk. The mammary glands are directly connected with abdominal cavity via inguinal canal by a pair of narrow oblique passages that allow blood and lymph vessels and nerves.

The udder of a good milch cow should have the following characteristics:

• The udder should be large enough to produce large vol­ume of milk and should have a good udder attachment.

• The desirable shape of the udder should be long, wide, and moderate in depth with evenly balanced and symmetrical udder quarters.

• The udder should extend well forward.

• It should have a reasonable height from floor level.

• The rear attachment should be high and wide.

• It should be soft to touch and have good mammary vein.

25.1.1.2 Teats

Milk from each gland is emptied through cylindrical or conical-shaped teats (Papilla mammae). Usually, only one teat drains one gland hence bovines have four teats. No sebaceous or sweat glands are found in the teat wall. Super­numerary teats or extra teats are found in 50% of cows which are generally removed before 1 year of age. The pseudo-teats are having no internal streak canal hence no connection to the internal structures of the gland. A good teat should be of moderate size, having proper placement and enough tension on the sphincter muscle around the teat orifice to allow easy milking and prevent leakage of milk.

25.1.2 Supporting Structures of the Udder

Supporting or suspensory structure of the udder is required to maintain proper udder attachment with the body as the weight of lactating mammary gland of a Holstein cow is around 50 kg (>100 lb). The mammary suspensory system is com­posed of six different types of tissues.

Skin (Tissue-I): The suspension capacity of skin is very low. Nevertheless, it plays a vital role in covering the mam­mary gland.

Fine areolar subcutaneous tissue or Superficial fascia (Tis- sue-II): It attaches the skin to the underlying tissue. It has poor suspension capacity.

Coarse areolar subcutaneous tissue (Tissue-III): This tissue is required to attach the front quarter with the body wall after forming a loose bond between abdominal wall and dorsal surface of front quarter.

Two parallel lateral suspensory ligaments (right and left lateral suspensory ligament) originate at the sub-pelvic tendons and travel vertically to cover exterior of the mam­mary gland. It is attached to the lateral surface of the udder with numerous lamellae and inserted into the glandular tissue and the connective tissue stroma to support lobules and lobes in the parenchyma. The lateral suspensory ligaments are made of fibrous tissues mainly collagen which is non-stretchable. Therefore, it provides main sus­pensory support to the udder without elasticity. There are two layers of lateral suspensory ligaments.

Superficial layer of lateral suspensory ligaments (Tissue-IV): It originates from sub-pelvic tendon and moves downward and forward to reach the udder. It covers the udder below the skin.

Deep layer of lateral suspensory ligament (Tissue-V): It is the inner part of lateral suspensory ligaments. It also originates from sub-pelvic tendon and is thicker than the superficial layer.

Median Suspensory Ligament (Tissue-VI): With the greatest tensile strength and being located in the body’s center of gravity, the median suspensory ligament is the main supporting system of the udder in cow. It is composed of two heavy yellow elastic sheets attached to the medial surface of the udder. Unlike lateral suspensory ligaments, it has elastic property and allows the mammary gland to stretch when fills with milk. The loosening of the ligament leads to pendulous udder.

Sub-pelvic tendon (Tissue-VII): It is not a part of udder suspensory system but it gives rise to superficial and deep lateral suspensory ligaments.

25.1.2 Internal Structure of the Udder

The udder is composed of two types of tissues. The paren­chymal or secretory tissues are composed of alveoli and ducts. The connective tissue supports the secretory tissue.

25.1.3.1 Alveoli

The primary secretory units of the mammary gland are alveoli.

The secretory epithelium of the mammary gland is cuboi- dal to columnar in nature that forms the peripheral lining of each alveolus. The secretory epithelium is responsible for the synthesis and secretion of milk. They absorb the blood precursors for milk constituents from adjacent capillaries and the milk is released in the lumen of the alveolus.

The mammary epithelial cell is composed of cytoplasm together with the organelles (nucleus, rough endoplasmic reticulum, mitochondria, and Golgi apparatus) covered by plasma membrane. Rough endoplasmic reticulum is situated adjacent to the basement membrane near nucleus. The Golgi apparatus is situated between the nucleus and the apical membrane. Secretory vesicles are present in Golgi apparatus as terminal swellings and contain casein. Fat is synthesized in the rough endoplasmic reticulum stored in fat droplets. Both, the fat droplets and the secretory vesicles are channelized towards the apical membrane guided by microtubules (situated perpendicular to plasma membrane) and secreted at the lumen. The cytoplasm is also populated with mitochondria and ribosomes.

Myoepithelial cells: These are modified smooth muscle with long cytoplasmic projections that surrounds each alveo­lus and small ducts. Due to their long cytoplasmic projections, they are also termed as basket cells. Myoepithelial cells have the ability to contract in response to oxytocin which allows the squeezing of epithelial cells and facilitates milk secretion into the lumen of alveoli.

25.1.3.2 Duct System

The duct system carries the milk from the secretory tissue to the teats. The ducts are composed of a double-layered epithelium surrounded by myoepithelial cells.

The arrangement of the ducts varies between species depending on the number of openings per teat. Cattle, buf­falo, sheep, and goats have one opening per teat hence they have only one final duct per gland. Mare and sows have two main ducts and associated openings. Dogs and cats have 10 or more openings per teat containing 10 or more final ducts.

25.1.3.3 Gland Cistern (Sinus Lactiferous or Udder Cistern)

The major ducts open in the gland cistern. It serves as the storehouse of milk between inter-milking periods. Generally, it is circular in shape but sometimes it may appear as pockets of various sizes at the terminal of major ducts. The capacity of the gland cistern varies from 100 to 400 mL.

25.1.3.4 Teat Cistern (Sinus Papillaris)

The cavities within the teat are termed as teat cistern. Teat cistern originates from the gland cistern and is continuous with the gland cistern. At the junction between the gland and teat cistern, there is a constriction called an annular fold composed of dense connective tissue with a thickness of 2-6 mm. Sometimes a horizontal septum forms at the annular fold and blocks the milk flow from gland cistern to teat cistern leading to a blind quarter and requires surgical interventions to correct it. The teat cistern is layered by double-layered epithelium consisting of columnar (luminal) and cuboidal (basal) cells. The storage capacity of teat cistern is 10-50 mL.

25.1.3.5 Streak Canal (Ductus Papillaris)

The distal opening of the teat cistern is called streak canal or teat canal through which milk is let down.

25.1.3 Blood Vascular System of the Mammary Gland

The mammary gland derives the precursors of milk from blood. In a high-yielding cow, 400-500 units of blood are required to synthesize one unit of milk with an average blood flow rate of 280 mL/s. The lactating udder receives 8% of the total blood volume. Thus, to meet this huge demand, the mammary gland must have a well-developed blood vascular system.

25.1.4.1 Arterial Supply

Arterial blood from the heart flows initially through posterior dorsal aorta which after entering into the abdominal cavity becomes abdominal posterior dorsal aorta. This aorta runs parallel to vertebral column and at the level of sixth lumber vertebrae, it diverges to form right and left iliac arteries and later into the internal and external iliac arteries. The external iliac artery gives rise to the external pudendal artery or mammary artery and reaches the dorsal surface of the udder via the inguinal canal. After emerging from the inguinal canal, mammary artery and associated milk vein follow a

S-shaped route which allows the lengthening of the blood vessels during the stretching of median suspensory ligaments during distension of the udder. The mammary artery forms subcutaneous abdominal artery which in turn divides into anterior and posterior mammary arteries. The subcutaneous abdominal artery supplies to the anterior dorsal portion of each side of the udder. The anterior and posterior mammary arteries vertically enter into the parenchyma of the fore and rear quarters of each side and terminate in a capillaries network surrounding the alveoli. The teats receive blood supply from papillary arteries which arise from mammary arteries. At the teat, papillary artery and venous plexus form corpus cavernosum.

25.1.4.2 Venous Drainage

Veins leaving the mammary gland run anti-parallel to the arteries. There are three veins to carry blood away from the mammary gland.

External pudic vein (middle mammary vein) runs parallel to the external pudic artery and joins the external iliac vein after ascending through the inguinal canal. The external pudic vein follows a route similar to that of the artery but the flow of blood is in the reverse direction.

Subcutaneous abdominal vein (milk vein/anterior mam­mary vein) leaves the mammary gland at the anterior end of the front quarters and runs along the abdominal wall. This vein is visible under the skin on the abdomen of the cow. It enters the body cavity through a depression at the xiphoid process called as “milk wells” and empties into internal thoracic vein.

Perineal vein (posterior mammary vein) drains the rear halves of the gland parallel to the perineal artery in an upward and backward direction. After turning the ischial arch it joins the internal pudic vein.

A venous circle is formed by anterior and posterior mam­mary veins to prevent venous outflow when the cow is lying down.

Papillary veins drain the teat and communicate with mam­mary veins upon the venous circle at the base of the udder.

25.1.4.3 Lymphatic System of the Udder

The main function of the lymphatic system is to circulate interstitial fluids originating from the capillaries of mammary parenchyma and to carry waste products away from the udder. Majority of the afferent lymphatic ducts converge to form larger lymphatics and run toward the dorsal portions of the udder. They terminate at the supra-mammary lymph nodes situated on the right and left halves of the udder. Around 1-7 numbers of supra mammary lymph nodes are situated above the caudal border of the mammary gland and their sizes range from 4 to 10 cm. The branches of the lymphatic vessels then pass through inguinal, iliac, and pre-femoral lymph nodes that join the lumbar lymph trunk and thereby continue to the thoracic duct to drain their con­tent at the anterior vena cava.

High-yielding cows often experience udder edema due to the accumulation of fluid between skin and glandular tissue during the periparturient periods. The etiology of udder edema is due to the imbalance of hydrostatic and osmotic pressures which result in fluid flow out of the capillaries into the interstitial spaces. Increased capillary permeability due to the damage of the capillary wall and obstruction of the lymphatic system is also the predisposing factors behind udder edema. Massage of the udder in the direction of supra-mammary lymph nodes is used to correct udder edema which allows the movement of lymph towards supra-mammary lymph nodes (as the movement of lymph is always in dorsal direction towards supra-mammary lymph node) and prevents the accumulation of lymphatic fluids.

25.1.4.4 Nerve Supply to the Udder

The sensory or the afferent nerves of the udder carry the information from the udder to the brain and involve in the initiation of the milk ejection reflex. The motor supply to the udder is entirely autonomic or sympathetic and composed of motor fiber to the smooth muscles of arterial walls and teat sphincter. They control the blood flow to the udder by alter­ing the diameter of the blood vessels and involved in the inhibition of the milk ejection reflex.

The main spinal nerves to the udder are the first, second, third, and fourth lumbar nerves and the external spermatic nerves. The first lumber nerve supplies the anterior portion of the udder without parenchyma. The second, third, and fourth lumber nerves fuse together to form inguinal nerve. The caudal portion of the udder is supplied with perineal nerve which is composed of the nerve fiber from second, third, and fourth sacral spinal nerves. Innervation of the udder is highest in the dermis of the teats. The terminal ending of these innervations are sensitive to physical stimuli like pressure, touch, and stretching.

The neurons of the sympathetic nerve fibers are located in the lateral horns of the spinal cord. The circular smooth muscles undergo continuous rhythmic contraction between milking relax at the time of milking allowing dilatation of teat canal and for milk flow in response to sympathetic nervous control.

25.1.4 MammaryGlandImmunity

Mammary gland protects itself from invading pathogens by means of anatomical, cellular, and soluble defense factors that act in coordination with each other. The defense mecha­nism of the udder is one of the prime area of research in the field of lactation physiology as mastitis or udder infection is the costliest disease in dairy cows. In addition, detailed knowledge on udder immunity will help to develop early detection kits for mastitis diagnosis and to develop appropri­ate therapeutic interventions. The immune components of mammary glands are either blood origin or locally synthesized factors together with udder morphology.

25.1.5.1 Anatomical Defenses

The first line of mammary gland defense is mediated through teat and associated structures. The sphincter present in the streak canal restricts the entry of pathogens during the inter­milking periods. The Furstenberg rosette at the internal end of the streak canal acts as a mechanical sealant against the entry of pathogens as well as local immune defense due to the localization of neutrophils around the rosette. Keratin secreted from the squamous epithelium at the streak canal also has bacteriocidal properties. The teat canal also acts as the physical barrier against pathogens by the peristaltic action of the smooth muscle lining of the teat canal. Rounder and pointed teats were reported to be more resistant to intramammary pathogens compared to flat, funnel-shaped, and cylindrical teats.

25.1.5.2 Cellular Defense

The cell populations in the mammary glands are collectively called as “milk somatic cells” (SCC) which are basically body-derived cells composed of mammary epithelial cells (70-75%) and leukocytes (25-30%). The leukocytes mainly comprise of polymorphonuclear neutrophils (PMN) (15-17% of total SCC), macrophages (20-21% of total milk SCC), and lymphocytes (46-60% of total milk SCC). Milk somatic cells are used as an indicator of udder inflammation and milk quality throughout the world. In a normal healthy quarter, the total somatic cell populations are below 100 ? 10³ cells/ mL of milk. But udder injury or inflammation leads to the migration of leukocytes to the site of infections and the leukocytes escape from capillary to alveolar epithelium and penetrates the basement membrane. During their penetration through basement membrane, epithelial cells are also sloughed off. Thus, during intramammary infection, SCC may increase up to several folds.

The roles of different cell populations are summarized in Table 25.2.

25.1.5.2.1 Factors Affecting Milk SCC

Mastitis or intramammary infections: Mastitis or intramammary infections are the main factors that lead to increased milk SCC. Milk SCC from an individual quarter depends upon the infection status of the quarter and SCC ≤ 100,000 cells/mL could be considered as threshold or negative for the California mastitis test. The increased milk SCC during mastitis is due to the efflux of PMN from blood.

Species: The buffaloes are reported to have low milk SCC compared to cattle whereas goats have higher milk SCC. The values of milk SCC in different species have been presented in Table 25.3.

Stage of lactation: It has been reported that SCC increases with progressing lactation regardless of whether the cow is infected or not.

Breed: SCC variation has been noted between breeds of dairy animals. Generally, SCC is higher in high-yielding cows compared to low yielders. The milk SCC in different breeds of cattle has been presented in Fig. 25.1.

Age and parity: Various researchers have reported that SCC increases with increasing age and is primarily due to an increased prevalence of infection in older cows. Young primiparous cows have less SCC due to less milk produc­tion compared to multiparous cows.

Milk yield: There is an inverse relationship between milk yield and milk SCC. High-producing cows have lower

Fig. 25.1 Milk SCC in different breeds of cattle. (Source: Alhussien and Dang 2018)

Table 25.3 Milk SCC in different species

Source: Mukherjee and Das (2019)

SCC followed by Escherichia coli and Streptococcus agalactiae.

Diurnal variations: both diurnal and infradian rhythmicity in milk SCC have been studied in cows. There was no significant diurnal variation in milk SCC in the cows with less than fourth parity. However, a significant diurnal variation in the DLC was recorded in the cows above fourth parity.

Managemental factors: There are many management factors that play the most important role in the development of contagious disease like mastitis in dairy animals. Among these, unhygienic conditions are more important in increasing the chances of intramammary infection (IMI) and resulting in high SCC. Teat injuries and leakers com­monly develop because of stall and platform design rais­ing the incidence of mastitis and causing higher SCC. The supplementation of antioxidant vitamins (Vitamin A, C, and E and β-carotene) and minerals (selenium, zinc, and copper) were reported to reduce milk SCC in cows. Cows treated with melatonin have been reported to possess improved milk quality and enhanced immunity. A vaccine against S. aureus named MASTIVAC I was reported to improve udder immunity and reduce milk SCC.

25.1.5.3 SolubleZHumoral Defense Factors

Soluble defense mediated by secreted antibodies, comple­ment proteins, and certain antimicrobial peptides. Majority of these defense mechanisms are originated from blood and extracellular fluids. Important humoral defense factors concerned with mammary gland immunity are described in Table 25.4.

25.2