MAMMARY GROWTH AND DEVELOPMENT

Involution

Dry Period

■ Period between milk removal cessation and

subsequent calving and lactation

■ Recommended duration: 45 to 60 days

■ Milk yield in next lactation decreases if:

– < 40 days

– > 80 to 90 days

Bovine Dry Period

Rat Dry Period

Why Do Cows Go Dry?

■ Suckling or milking required to maintain lactation

– Mammary gland stimulation results in oxytocin

secretion from the posterior pituitary

– Oxytocin travels via the blood to the mammary gland

and causes contraction of the myoepithelial cells

surrounding the alveolus

– Results in expulsion of luminal milk from alveoli into

ducts and out of the gland, resulting in the physical

removal of milk from the alveoli

■ Without frequent emptying of the mammary gland, milk

synthesis will not persist despite adequate hormones

■ Maintenance of consistent milking will not maintain

lactation indefinitely

Suckling

■ Rat mammary gland still in secretory state if teats

are ligated but suckling continues

■ Involution inhibited from one side (with ligated

teats) if suckling occurred on other side

■ Involution inhibiting effects of prolactin

■ What happens to a cow if not milked for short

periods of time?

FL Power Outage (5-6 milkings)

Involution Characteristics

■ Decreased metabolic activity of mammary gland

■ Decreased size and number of alveoli

■ Decreased total alveoli and lobule volume

■ Alveolar collapse

■ Regression of glandular tissue

■ Decreased number of organelles

– Mitochondria swelling (=degradation)

■ Increased numbers of:

– Cytosomes (vacuoles containing cellular debris)

– Cytosegrosomes (autophagic vacuoles containing

organelles and debris)

– Lysosomes

:Lactating

Dry:

Lactating

Involuting

Involution

■ Milk composition changes

– Rapid decline in lactose synthesis

– Total protein concentrations increase in early involution,

partially because of water resorption from the secretion

and partly due to increased concentrations of lactoferrin,

serum albumin, and immunoglobulins

– Lactoferrin synthesis increases in contrast to milk-

specific proteins (e.g. casein) whose synthesis decreases

■ Lactoferrin has a number of potential functions in the

mammary gland, particularly as a nonspecific

disease resistance factor

– Iron-binding protein, thought to compete with

bacteria for iron (bacteriostatic)

Secretory Changes in Bovine Dry Period

Milk Components Active Involution Steady State

Involution

Redevelopment

/Colostrogenesis

Lactose Decreasing Low Increasing

Protein Decreasing Low Increasing

Fat Decreasing Low Increasing

Total volume Decreasing Low Increasing

Leukocytes Increasing High Low

Lactoferrin Increasing High Low

Immunoglobulins Increasing High Increasing

Structural Changes In Cows■ Changes in bovine mammary cells begin within 48 hours

after cessation of milk removal

– Formation of large stasis vacuoles in the epithelial

cells, a result of intracellular accumulation of milk fat

droplets and secretory vesicles

■ Alveolar lumenal area declines, while interalveolar stromal

area increases

■ Fluid volume in the gland decreases between day 3 and 7

of involution

■ Collapsed alveolar structures remaining are considerably

smaller than during lactation by day 28, with a very small

lumen

■ General alveolar structure is maintained throughout

involution

Structural Changes In Cows

■ No extensive tissue degeneration like other species

(e.g. rodents)

■ Change in secretory state rather than a change in

tissue regression

■ Possible cause: Cows are typically pregnant during

involution and pregnancy might play a role in the

inhibition of epithelial cell apoptosis

– But we don’t completely know if inhibition of

apoptosis is the role pregnancy plays on involution

– Apoptosis = programmed cell death

■ Necrosis = cell death from pathological cause

Changes In Cows: Summary

■ In summary, histological changes occurring in the involuting

bovine mammary gland involve:

– Little loss of alveolar epithelial cells

– Invasion of leukocytes

– Little histological evidence of apoptosis

– Increase in interalveolar connective tissue and

fibroblasts

– Increase in remodeling of the extracellular matrix

– Decrease in intra-alveolar area

– Decrease of cytoplasmic organelles involved in milk

protein synthesis (e.g., Golgi apparatus) and secretion

function (e.g., vesicles)

– Limited change in organelles with metabolic function

(e.g., ribosomes)

The Dry Period is a Working Vacation – Tissue Remodeling

Lactating cells

Involution

Lactating cell

Milk stasis

Autophagic process

Involuted cell

Cellular Migration

■ Very few cells (less than 2%) in mammary secretions

during involution are epithelial cells

■ Most cells are leukocytes

■ Total leukocyte concentrations in mammary secretions

increase rapidly in early involution

■ Types of leukocytes found in mammary secretions

during the dry period:

– PMN (polymorphonuclear neutrophils)

– Macrophages

– Lymphocytes

Cellular Migration

Cellular Migration

Cellular Migration

PMN

■ Phagocytic leukocytes

■ Predominant for the first 3-7 days

■ If quarter is also infected, they will predominate

throughout the early stages of infection

https://www.youtube.com

/watch?v=JnlULOjUhSQ

PMN migration

PMN migration

Macrophage

■ Predominant cell type after 7 days

■ Phagocytes

■ Ingest fat droplets and other debris

■ Play a major role in removing large quantities of fat

and cellular debris, including dead PMN

■ Also predominant cell type in the colostrum

Lymphocytes

■ Always present

■ B-cells become plasma cells (produce antibody)

■ T-cells aid in antibody response and cell-mediated

functions

■ Specific function in the involuting mammary gland

is not well known

Lymphocyte Riding a Macrophage!

New IntramammaryInfections During Early Dry Period■ Milk is no longer periodically removed from the gland

■ Milk is an excellent growth medium for bacteria

■ Accumulation of a large volume of milk in the gland (for the

first few days)

■ Milk leakage

■ Teat-end disinfection is stopped

■ Phagocytic Leukocytes (Somatic Cells) and Other Defenses:

■ Leukocytes begin entering the gland by day 1 after dry-off

– Busy ingesting milk fat, casein and debris