Lactation Physiology(part 1)

By: A. Riasi (PhD in Animal Nutrition &

Physiology)

فیزیولوژی تولید و ترشح شیر

What is a mammary gland?

Serves a reproductive function; nourishment of the neonate.

The mammary gland is one of a few tissues in mammals, which

can repeatedly undergo growth, functional differentiation, and

regression

Relies on same endocrine (hormonal) support for development

and function.

Example: gonadal steroids, prolactin, etc.

What is the difference between the animal udder?

Cow: Four glands and four teats

Sheep and goats: Two glands and two teats

Sow: 12-14 teats and two glands per teat.

Mare: Four glands and only two teats.

The udder is a complex system

A supportive system.

A secretory system composed of epithelial cells.

A duct system for storage and conveyance of milk.

Blood, lymph, and nerve systems.

The udder of cows

The weight of empty cows udder is about 12-30 kg.

The udder weight is affected by:

Age

Stage of lactation

Amount of milk in the udder

Inherited differences among cows

The supportive system of udder

There are seven tissues that provide support for the udder:

Skin covering the gland is only of very minor support.

Superficial fascia or Areolar subcutaneous tissue

Coarse areolar or cordlike tissue

Subpelvic tendon

Superficial layers of lateral suspensory ligament

Deep lateral suspensory ligament

Median Suspensory Ligament

An illustrated view of the ligaments that permit udder suspension (Courtesy of Iowa State University)

Teat structure

Interior anatomy of the Mammary Gland

The interior structure of mammary gland:

Connective tissue

Ductular system

Secretory tissue

Mammary duct system

Secretory tissue

Secretory tissue

A lactating secretory cell is the basic unit of milk synthesis

Milk precursors are taken from the blood into the cell

The secretory cell have two kind of junctions with neighbor cells:

Tight junction around the apical portion

Gap junction in lateral portion

Major component of a secretory epithelial cell

Nucleus

Endoplasmic Reticulum

Golgi apparatusSecretory vesicles

Lysosomes

Cytoplasm

Tight junctionGap junction

Basal and lateral membranes

Apical membrane

Basement membrane

Precursors of Milk

Precursors of milk come from the bloodstream and the primary

substrates extracted from blood include:

Glucose

Amino acids

Fatty acids

Minerals

Acetate *

βHB *

Precursors of Milk

Several materials in milk come unchanged from the blood:

Minerals

Hormones

Immunoglobulins

Synthesis of milk proteins

There are several specific systems for amino acids are

absorption through the basal membrane.

Inside the cell, amino acids are covalently bound together to

form proteins at the polysomes (Poly-ribosomes).

Proteins sythesized at RER include:

Casein

β-lactoglobulin, and α-lactalbumin

Membrane bound proteins

Synthesis of milk proteins

Synthesized proteins are transferred the golgi apparatues (GA).

Casein is secreted as micelle, which is formed in the GA from:

Casein molecues

Calcium

Phosphorus

Synthesis of milk lactose

Glucose enters the cells via the basolateral membrane via

specific transport system.

Some glucose is converted to galactose in the cell.

Both glucose and galactose enter the GA and react resulting in the

formation of lactose.

Synthesis of milk fat

In ruminant, acetate and β-hydroxybutyrate are important

precursors of fatty acids (FA) synthesis in mammary cells.

Preformed FA, glycerol and monoacylglyceride are absorbed at

the basolateral membrane.

Milk fat triglycerides are synthesized on the smooth

endoplasmic reticulum and form small droplet.

Synthesis of milk fat

Under certain circumstances, fat droplets fuse with each other to

form cytoplasmic vacuoles.

The protein coat on the milk fat globule membrane comprises:

Mainly butyrophilin (BTN) *

Xanthine oxidoreductase (XDH) *

Adipophilin (ADPH)

Mucin 1

CD36

Periodic acid/Schiff

PAS III, and FABP

Pathways for milk fat globule transit and secretion from mammary epithelial cells

Synthesis of milk fat

The properties of milk fat:

Milk fat composed of different fatty acids:

Short chains (4-8 C)

Medium chains (10-14 C)

Long chains (≥16 C)

More than 95% of milk fat is TAG

Around 70% of FA by weight in milk fat are saturated

Approximately 25% of the milk FA are monounsaturated

PUFA only account for a small portion of total FA in milk

Synthesis of milk fat

There are two sources of FA for milk fat synthesis:

The de novo FA synthesis in mammary epithelial cells

Short chain (4-8 C)

Medium chain (10-14 C)

About 50% of 16 C

Preformed FA uptake from blood circulation

De novo fatty acid synthesis

In ruminants, the substrates for de novo FA synthesis in

mammary epithelial cells are:

Acetate produced by rumen fermentation

β- hydroxybutyrate produced by the rumen epithelium

Preformed fatty acid uptake

Long-chain FA taken up by the mammary gland are imported

from plasma:

Released from circulating lipoproteins by lipoprotein lipase

NEFA bound to albumin

There is evidence showing that the membrane transport of long-

chain FA is a facilitated process.

Some factors might play a role in FA uptake and transport:

Cluster of differentiation 36 (CD36)

Fatty acid binding protein 3 (FABP3)

Properties of milk TAG

Fatty acids are not esterified randomly to the sn-1, -2, and -3

positions of glycerol backbone.

The distribution of FA is dependent on the distinct binding

affinities of the acyltransferase enzymes for substrate FA.

Milk fat depression (MFD)

Several theories have been proposed to explain the physiology

behind this reduction in fat synthesis.

Lower production of acetic and butyric acids in the rumen caused

less fat production in mammary gland.

The greater proportionate production in rumen increases the blood

insulin, which partitions nutrients away from the mammary gland.

A more current theory is that the combination of high grain and

high unsaturated fatty acids in the diet causes the microorganisms in

the rumen to produce more trans fatty acids.

Milk fat depression (MFD)

Avoiding milk fat depression

Proper cooling of cows

Control the amount of polyunsaturated fatty acids in the diet

Balance dietary carbohydrates

Buffer and alkalinizing agents

Ionophores

Feeding Management

Transport of milk components not synthesized in the

epithelial cells

Some milk components pass across the epithelial cell barrier

essentially unchanged:

Immunoglobulins

Serum albumim

Paracellular pathways for transport components

This occurs when substances and molecules are allowed to pass

through the junctional complexes.

This condition resulting in a change in electrical conductivity of

milk (used in detection of mastitis)

This condition increase concentration of lactose and other milk

components in the blood.

Mammary blood supply

Milk synthetic rate is depended to the rate of blood flow to the

mammary gland.

There is a 2-6 fold increase in blood flow in the mammary gland

staring 2-3 days prepartum.

The efficiency of extraction of the components from the blood

while it passes through the udder is very important.

Mammary blood supply

Mammary lymphatic network

The extracellular fluids are drained from the tissue and

conducted back to the circulatory system via the lymphatic

network.

The lymphatics contain concentrated areas of leukocytes

(particularly lymphocytes and macrophages) in lymph nodes

The lymphatic network serves to transport some things in the

body (vitamin K, lipids absorbed in the intestine).

Mammary lymphatic network

Mammary nervous system

The efferent innervation of the mammary gland is entirely

sympathetic in origin.

The efferent nerves innervate the muscle fibres within the

connective tissue surrounding the lobules, lobes, and the blood

vessels.

Mammary nervous system

Innervation of the udder is sparse compared with other tissues.

Sensory (afferent) nerves are involved in milk ejection and found

in the teats and skins.

Similar to other skin glands, there is no parasympathetic

innervation to the gland.

Sympathetic nerves are associated with the arteries but not with

alveoli.

There is no innervation of the secretory system.

Few nerves go to the interior of the udder.

Milk ejection

Oxytocin has the main role in milk ejection.

Oxytocin causes contraction of the myoepithelial cells.

Without frequent emptying of the mammary gland, milk

synthesis will not persist in spite of adequate hormonal status.

The time from the start of a tactile stimulation until the

occurrence of milk ejection spans between 40 s to >2 min and

increases with decreasing degree of udder filling.

Milk ejection

Milk ejection reflex actually is a neuroendocrine reflex.

The reflex has two pathways:

Afferent Pathway (neural)

Efferent Pathway (hormonal, blood-borne)

Milk ejection

Other mechanisms of milk ejection:

Myoepithelial cells will also contract in response to vasopressin

(ADH or antidiuretic hormone).

Visual or auditory stimuli can cause milk ejection. Milk ejection is

a condition response.

Stimulation of the genital tract such as vaginal distention causes

release of large amounts of oxytocin.

The mechanical tap stimulus does not involve oxytocin.

Effect of stress on milk ejection

Various stressful stimuli that inhibit milk ejection are associated

with increased activity of the sympathetic nervous system.

Role of autonomic nervous system

Sympathetic nerves, The neuroendocrine components of

sympathetic nerves are:

Epinephrine

Norepinephrine

Colostrum production

In mammals, colostrum is known to contain larger amounts of

specific proteins than milk:

Immunoglobulins

Antimicrobial peptides (eg, lactoferrin and lactoperoxidase)

Other bioactive molecules, including growth factors

Under certain circumstances, the maternal antibodies may also

attack and destroy the newborns red blood cells, thereby causing

fatal incompatability reactions known as hemolysis of the newborn

or neonatal isoerythrolysis (NI).

Immunoglobulin transport in the mammary gland

The IgG1 and IgG2 make up the majority of immunoglobulin in

cow colostrum and primarily come from the blood.

Most of the IgA and IgM that are transported into colostrum are

synthesized by the plasma cells (B lymphocytes) that reside in the

mammary tissue.

Transport of the IgGs and the IgA/IgM occurs through the

epithelial cells by a process involving small transport vesicles.

Intestinal protective factors in colostrums and milk

The gastrointestinal tract is constantly under attack from acid,

proteolytic enzymes, and ingested noxious agents, such as aspirin

or alcohol.

The presence of multiple defense mechanisms— including the

mucus-bicarbonate layer in the stomach, a rapid mucosal turnover,

and a good blood supply—ensure that the mucosa remains intact

most of the time.

Bioactive factors in colostrums and milk

Colostrum and milk contain many factors that can influence cell

growth, differentiation, and function:

Glutamine

Polyamines

Nucleotides

Galactopoeisis

Galactopoeisis is the maintenance of lactation once lactation has

been established.

Two key interrelated components contribute to the maintenance

of lactation:

Galactopoietic hormones

Prolactin

Growth hormone

Removal of accumulated milk

Galactopoeisis

Local mammary factors play a major role in regulating milk

secretion in many species.

Feedback inhibitor of lactation (FIL) found in milk. FIL is

thought to be produced by the mammary cells as they synthesize

and secrete milk.