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7-Biology of Lactation > Slide Set 6: Involution > Flashcards

Slide Set 6: Involution Flashcards

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1
Q

Define involution

A
  • The regression of the mammary gland following the end of a lactation cycle
  • The mammary gland returns to a non-lactating state
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2
Q

What are the characteristics of involution?

A
  • Decrease in mammary cell number and activity
  • Reduction in galctopoietic hormones (systemic factors)
  • Accumulation of local factors (inhibition of lactation)
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3
Q

When does involution begin?

A

Around 4-5 months after parturition

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4
Q

What are the main features of involution?

A

Ø A decrease in cell number due to cell death
(apoptosis)
Ø A decrease in cell activities duo to tissue remodelling

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5
Q

What are the types of involution?

A

1-Gradual involution
2-Initiated involution
3-Senile involution

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6
Q

What is gradual involution and how does it occur?

A

Ø Occurs during normal lactation
Ø Results in gradual reduction in milk production
throughout lactation (i.e. less suckling)
Ø Decline in hormonal stimulus (galactopeiotic hormones)
Ø Accumulation of milk and local inhibitory factors in the mammary gland

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7
Q

What is initiated involution and how does it occur?

A

Ø Induced by humans on domestic animals
Ø sudden cessation of milk removal
Ø Changes in the mammary gland tissues more abrupt than changes observed during gradual involution
Ø Example: dry period in dairy cows
Ø Both gradual and initiated involution are reversible if
pregnancy occurs

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8
Q

What is senile involution and how does it occur?

A
  • irreversible involution

Ø Occurs at the end of the reproductive cycle of the female (aging)

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9
Q

What is complete involution?

A

Ø Complete involution: rapid loss of secretory functions; complete loss of the epithelial secretory cells (virgin-like mammary gland)
Ø Epithelial cell components are degraded by lysosomal enzymes released into the cytoplasm
Ø Complete involution is common in some mammalian species such as rats and mice

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10
Q

What is incomplete involution?

A

Ø Incomplete involution: collapsing of the alveolar structure but the secretory cells are still intact (e.g. dairy cows)

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11
Q

What are the changes that occur during involution?

A
  • Changes in mammary tissues
  • Changes in mammary cell secretions
  • Changes in mammary cell organelles
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12
Q

What are the changes in mammary gland during involution?

A

Ø Progressive regression from the peripheries towards the gland cisterns
Ø Entire lobes & lobules degenerate instead of single epithelial cells

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13
Q

What are the changes in mammary gland during involution (cow)?

A

Ø Decrease in alveolar size
Ø Decrease in # of alveoli per lobule
Ø Decrease in # of secretory cells per alveolus
Ø Reduction in luminal volume
Ø Connective tissue become more prominent
Ø Limited disengagement of epithelial cells from basement membrane (unlike rodents)

Despite the fact that the lobular structure is reduced, it is still recognizable (unlike virgin mammary gland)

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14
Q

What are the changes in milk volume during involution?

A
  • Accumulation of milk in mammary cell
  • Increased intra-mammary pressure
  • Rupture & damage of the basement membrane
  • Milk moves into interstitial space
  • Milk components broken-down by phagocytosis
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15
Q

What are the local factors that are responsible for milk inhibition?

A
  • milk accumulation
  • FIL
  • Serotonin
  • Lactoferrin
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16
Q

What is the role role of plasminogen / plasmin in involution

A

Ø ensures normal functioning of the circulatory system
Ø maintains lumen fluidity in vascular system by cleaving excessive / unwanted clots (fibrin)
Ø Widely distributed in the body
Ø In mammary gland the concentration of plasominogen / plasmin increases as lactation progresses

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17
Q

What is the role of role of serotonin in involution?

A
  • Potent inhibitor of lactation (rats, women, bovine)
  • Immune response
  • Junctional disruption (tight junctions)
  • Cells death
  • Inhibits milk protein synthesis
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18
Q

Explain the changes in milk volume during involution (cows)

A

Ø Milk volume increases during the first days of involution
Ø Milk volume declines substantially between day 3-7 following cessation of milk removal
Ø Further reduction occurs by day 30

19
Q

What happens to the cell organelles during involution?

A

Ø Milk synthesis in the mammary secretory cell stops within 48 h after cessation of milk removal
Ø Appearance of large vacuoles after 48 h of milk cessation
Ø Vacuoles are formed by the fusion of secretory vesicles & fat droplets
Ø Organelles involved in milk biosynthesis (Golgi apparatus & RER): Almost disappear 48 hours following cassation of milk removal
Ø Mitochondria, ribosomes, nucleus: remain intact throughout involution

20
Q

Which organelles remain intact during involution?

A

Mitochondria, ribosomes, nucleus: remain intact throughout involution

21
Q

Explain the changes in milk constituents during involution

A

Ø Milk specific components decline
Ø Blood serum components increase
Ø Milk fat and lactose decrease
Ø concentration of total protein increases in early days of involution (high lactoferrin and high serum albumin)
Ø Milk export proteins (casein, α-lactalbumin, β- lactoglobulins) decreases
Ø Concentrations of other serum proteins (lactoferrin, immunoglobulins) increases

22
Q

What happens to the lactoferrin during involution?

A

Ø iron-binding protein secreted by the mammary gland
Ø Synthesis of lactoferrin increases during milk stasis
and involution (~100 fold)
Ø Synthesis declines after ~14 d of involution
Ø Suppresses casein expression (inhibits secretion)
Ø Effect of lactoferrin on involution is reversible (based on duration of milk stasis)
Ø antibacterial properties
Ø Lactoferrin is higher in human milk than in cow milk

23
Q

What happens to the leukocytes during involution?

A

Ø Leukocytes # in secretion increase during early involution and remain elevated (non-inflammatory reaction
Ø Involve in phagocytosis of residual milk constituent
Ø Involve in protecting the mammary gland from bacterial invasion

24
Q

What happens to the leukocytes (phagocytes) during involution?

A

Ø Play a major rule in removing fat droplets, cellular debris
ØTwo types
1-Neutrophils (polymorphonuclear)
ØDominant during the initial few days of involution
2-Macrophages & lymphocytes (mononuclear)
ØDominate after neutrophils

25
Q

What are the two types of phagocytes that are found in milk contituents? What are their functions?

A

1-Neutrophils (polymorphonuclear)
ØDominant during the initial few days of involution

2-Macrophages & lymphocytes (mononuclear)
ØDominate after neutrophils

26
Q

What happens to the lysosomal enzymes during involution? Give examples

A

Ø Activities of several lysosomal enzymes increases during involution

Example:
Ø Lactoperoxidase
Ø Proteases
Ø Plasminogen activators

27
Q

Involution in rodents (complete involution) is characterized by:

A

Ø Rapid loss of tissue function
Ø Degeneration of alveolar structure
Ø Massive loss of epithelial cells (>50%) Involution remains reversible for 30-36 h
Ø The cell loss is due to programmed cell death (apoptosis)

28
Q

What is apoptosis?

A
  • Programmed (active) cell death
  • Cell shrinks, losses contact with neighboring cells and displays intracellular protein on its surface
  • Chromatin condenses and DNA cleaved into small fragments
  • Small membrane bodies break off containing intracellular materials (apoptotic bodies)
  • Secondary necrosis (breakdown) will follow
29
Q

What is necrosis?

A
  • Uncontrolled (passive) cell death
  • Cell swells and mitochondria is damaged (rapid energy depletion)
  • Breakdown of homoestatic control
  • Cell membrane lysis and release of cellular contents
  • Inflammatory response and damages to surrounding cells
30
Q

Explain the involution in rodents

A
  • A rapid process (8-10 days) where the epithelial cells of the lactating gland is returned to a rudimentary state (virgin-state)
  • Can be divided into 2 stages (based on reversibility):
    1- Reversible stage (2 days): Gland can return to lactating state if suckling is re-introduced
    2- Irreversible stage(3-10days): Gland is unable to return to lactation without being re-stimulated by pregnancy
31
Q

What are the 2 stages of involution in rodents? What is it based on?

A
  • Can be divided into 2 stages (based on reversibility):
    1- Reversible stage (2 days): Gland can return to lactating state if suckling is re-introduced
    2- Irreversible stage(3-10days): Gland is unable to return to lactation without being re-stimulated by pregnancy
32
Q

What are the detailed categories of involution in rodents?

A

1- Milk stasis (inhibition)
2- Epithelial regression (via cell death)
3- Immune response and clearance of debris
4- tight junction and barrier disruption
5- Extra cellular matrix (ECM) remodeling
6- Adipose tissue remodeling
7- Vascular remodeling

33
Q

Define dry period

A

Period between the end of one lactation and the start of the next (2 month prior to parturition or calving)

34
Q

What does life of a cow look like

A

Calf –> Bred (14-18 months) –> 1st calving (23-25 months) –> dried off (305-320 days in milk) –> calf for 2nd time –> calf or culled re-bred

35
Q

Explain the lifecycle of cottontail rabbit

A
  • Becomes pregnant immediately after parturition
  • Pregnant and lactate for 18 days
  • Dry period of 8-10 days after weaning
  • Cycle is repeated 4-6 times a year
  • Rarely repeated for more than 2 seasons
36
Q

What is the importance of dry period?

A

Ø Allow mammary gland to go through a period of Involution
Ø Ensures maximum number of secretory cells in Early lactation
Ø Minimize metabolic disorder

37
Q

What are the characteristics of unique involution?

A
  • Involution during the dry period in markedly less than in other species
  • Few epithelial cells are lost, no detachment of cells from basement membrane
  • Area occupied by epithelium does not change and alveolar structures remain intact
38
Q

What are the justifications for the dry period?

A

1- Old cells produce less milk than new cells
2- Life span of old cells is shorter than new cells
3- # of proliferative cells will increase during the dry period

39
Q

What are the stage of drying-off?

A

Ø Build-up of intra-mammary pressure
Ø Rapid decline of lactose biosynthesis (within few
hours)
Ø Water transportation to the epithelial cells stops
Ø Aveolar and lumenal areas decline (within 7 days)
Ø Aveolar system considerably collapses by day 28 but does not disappear

40
Q

Physiology of the mammary gland during the dry period can be divided into three phases:

A

1- Active involution
2- Steady state involution
3- Redevelopment and colostrogenesis

41
Q

Explain active involution

A

Ø Transition phase from lactating to non-lactating stage
Ø Duration: 21-30 days
Ø Changes in milk constituents, cell organelles and cell Secretions (discussed earlier)

42
Q

Explain steady state involution

A 
Ø Transition between active involution &re- development
Ø Little fluid in the gland
Ø High concentrations of leukocytes
Ø Little milk fat or casein debris left 
Ø Immunoglobulin concentrations are high
43
Q

Explain redevelopment and colostrogenesis

A

Ø Transition between non-lactating to lactating phase
Ø Begins 3-4 weeks prepartum
Ø Selective increase in uptake of immunoglobulins
Ø Increased concentrations of milk components (~2 weeks pre-partum, increased markedly 3-5 pre- calving)

7-Biology of Lactation (16 decks)

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