Mammary Gland Development

Suporn Katawatin
Department of Animal Science
Faculty of Agriculture
Khon Kaen University

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Mammary gland

One of a few tissues in mammals

which can repeatedly undergo
cycles of growth, functional
differentiation, and regression

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Mammogenesis

„ term used for development of the

mammary gland
„ refers to development of mammary
gland structures

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Mammary development
„ begins early fetus and proceeds beyond initiation of
lactation

1. Prenatal (Fetus)
2. Prepubertal
3. Postpubertal
4. Pregnancy or gestation
5. Early lactation

Involution & Dry period

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12 months old heifer

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Heifers, ~6 months pregnant

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 Primigravid heifer
1-2 weeks prepartum

Older cow
1-2 weeks prepartum
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Fetal Mammary Development
„ hormone is not necessary
„ similar structures in male and female
„ only basic structures develop
„ development occurs at first half of
pregnancy
„ very little further development before birth

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Fetal
Mammary
Development

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Fetal Mammary Development
„ Thickening of ectoderm on both sides of midline
‰ 'mammary band' and 'mammary line’ (30 days fetus)

‰ Mammary buds form along mammary line

(correspond to number of glands in adult)

„ Mammary buds 'sink' into mesenchyme

‰ teat meatus, teat and gland cisterns, and the duct

system: the primary sprout

„ Primary sprout canalized and becomes secondary

sprouts : major ducts of the mammary gland
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Fetal mammary gland development (cont.)

33 day-old bovine
embryo (red arrow)
time that trophoblast
membranes attach to
endometrium
embryo has only just
formed its mammary
band

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At Birth - the followings are observed:
„ Teats well developed
„ Secondary sprouts canalized, but solid core of cells at
the end (will continue to grow and branch)
„ Growth of the sprouts is limited to the area around the
gland cistern
„ Non-secretary tissue well formed (connective tissue,
blood vessels, lymph vessels)
„ male gland similar, but not fully developed
„ Secretary or glandular parts are not developed at this
time
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Mammary Development: Birth to Puberty

„ Extensive growth; increase in connective tissue

and deposition of fat

‰ Birth to three months - isometric growth;

parallels growth of other tissues (by DNA
content)

‰ Three months to puberty; allometric growth;

increase in DNA content is greater than in
other tissues

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Birth To Puberty (cont.)

„ Ducts continue to grow and shape as in mature udder

„ Udder increase both weight and capacity

‰ There is deposition of adipose tissue; front and rear

quarters approach each other

‰ DNA increases (increased mammary cell numbers) are

maximal from 2-3 months to 9 months

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Birth To Puberty (cont.)

„ Overfeeding heifers reduces subsequent

mammary cell numbers

‰ reduce milk production for entire life

‰ increase parenchymal fat in udder

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Figure 2. Mammary growth in heifers

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Mammary Development: Postpuberty

‰ After puberty, each recurring estrous cycle

further mammary gland development

‰ Hormones influenced
„ Estrogen : duct growth

„ progesterone : secretary tissue development

‰ Also prolactin, somatotropin

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Recurrent Estrous Cycles

‰ Growth of buds and branches from

secondary and tertiary sprouts

‰ Final buds develop into alveoli

(may not occur prior to pregnancy: may only be

small ducts)

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Recurrent Estrous Cycles : Prior to Estrus

„ Increase duct system growth

‰ estrogenic phase of the cycle

‰ some lost after estrus (during diestrus)

„ Alveolar lumen enlarges and contains secretions

‰ Epithelial cells become cuboidal and shrink during

diestrus as do alveoli
‰ Mitotic activity greatest on day of estrus and
declines during diestrus

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Recurrent Estrous Cycles : Prior to Pregnancy

„ Epithelial layers of ducts and alveoli as during

lactation

„ Majority of mammary tissue is adipose

„ In heifers; increases in ducts system occur

during first few estrous cycles; then plateau
until conception
‰ No true alveoli are evident until pregnancy

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Mammary development: Pregnancy

„ Marked increase in mammary gland growth

‰ Most of the duct growth occurs during the 1st part
of pregnancy
‰ Lobuloalveolar system form during the middle and
latter parts of pregnancy

„ Big growth occurs during pregnancy then regresses

after the peak of lactation
„ cycle repeats itself with each pregnancy and
lactation period
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During Pregnancy (cont.)

„ Gland cistern increase in 5th and 6th months

„ 4th to 7th months, glandular proliferation
increase near large ducts entering the gland
cistern
„ Further branching of small ducts

„ Formation of end buds

„ Secretary tissue replaces adipose tissue

and forms small lobules
„ Alveoli are differentiated from ducts

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During Pregnancy (cont.)

„ Connective tissue separates lobules and

lobes, containing abundant blood
capillaries

„ 6th -9th months, marked increase in

growth of duct secretary tissue, vascular
system and lymphatics

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During Pregnancy (cont.)

„ 9th month, alveoli initiate some secretary activity

‰ Epithelial cells become distended
‰ Fat droplets are present
‰ Cytoplasm becomes granular
‰ Some fat droplets accumulate in lumen of
alveoli and create distention

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Mammary development: During Pregnancy

„ In conclude
‰ Greatest mammary growth completed during
first half of pregnancy, but growth continues
to parturition
‰ Recurring pregnancy increases mammary
gland growth up to mature size

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Hormonal Regulation of Mammary
Development During Pregnancy

„ Further reading at
MamPregnancyHormone.doc

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Mammary development: During
Lactation

„ Some additional growth occur after

parturition (between parturition and
peak lactation)

‰ 65% increase in mammary DNA

between 10 days prepartum and 10
days postpartum
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During Lactation (cont.)

„ Mammary DNA maximum at peak lactation

(45 days)
‰ Cells per alveolus double at time of
parturition

„ after peak, very little cellular proliferation

‰ cells destroyed and lost through milk

‰ not replaced by mitosis through declining

stages of lactation
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During Lactation (cont.)

„ Lactating and pregnant cattle

‰ milk yield and tissue DNA reduced after 5th

month of pregnancy compared to open cattle

„ Similar trends seen in other species

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in sows: mammary growth during lactation

„ role of nursing intensity

„ role of relaxin during pregnancy,
‰ removal of relaxin during late pregnancy reduce
mammary development at the time of parturition
‰ But stimulated by nursing of the young

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 Involutionary Process
„ Characterized by:
‰ Decreased metabolic activity of mammary gland
‰ Decreased size of alveoli
‰ Decreased number of alveoli/lobules
‰ Decreased total alveoli and lobule volume
‰ Decreased number of cells/alveoli
‰ Temporary increase in height of alveolar cells
‰ Alveolar collapse; disintegration
‰ Connective tissue
„ does not proliferate
„ more obvious because of regression of glandular
tissue
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Involutionary Process (cont.)

„ Ultrastructural changes during involution

‰ Removal of protein granules from milk by digestion of

vacuoles by lysosomes
‰ Necrosis of epithelial cells
‰ Phagocytosis of cellular debris and fat droplets
‰ Detachment of epithelial cells
‰ Invasion of adipose tissue into parenchyma
‰ Myoepithelial cells remain intact
‰ Normally, no increase in leukocytes in involuting
tissue; no inflammatory reaction
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 Dry Period

„ mammary gland of dairy cow requires

nonlactating (dry) period prior to coming
parturition to optimize milk production in
subsequent lactation

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Dry Period

„ time between halting of milk removal and

subsequent calving
„ 45 to 50 days is recommended
„ If less than 40 days milk yield decreased in next
lactation
„ over 70 or 80 days lowered production in next
lactation
„ see Swanson (1965); Coppock et al. (1974); Dias and Allaire,
(1982)
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Dry Period

„ may not be required for goats (see Fowler et al.

1991)
„ requirement for a dry period between
lactations may be peculiar to the dairy cow.
‰ consider that most species are not concurrently
pregnant and lactating (they exhibit some level of
lactational anestrus or other inhibitory effect of
lactation on reproductive function). Therefore,
they only start reproductive cycling after weaning
(the end of lactation), so there indeed will be a
nonlactating period prior to the next parturition.
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Dry Period and Mastitis

„ early dry period ( first week or two) is the

highest incidence of new intramammary
infection
„ mid-dry period is the lowest incidence of new
IMI
„ peripartum period is also a time of high
incidence of IMI

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Mammary Physiology during dry period

„ Further reading at MamPhysioDryPeriod.doc

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 Cow : Embryonic development

¾ 1st month - a layer of cuboidal cells form from

ectoderm; differentiates from underlying
mesenchyme
¾ Mammary line begins about 4-5 weeks
¾ Then to mammary crest, mammary hillock,
mammary buds
¾ At 45 days old embryo, two buds form on each line;
fore and rear quarters of each udder half

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 Cow : Embryonic development

¾ Cells proliferate to form a spherical shape

and sink into mesenchyme, may sink entirely
leaving only a small depression which
eventually elongates to form streak canal
¾ Males and females comparable in growth to
this point

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 Cow : Teat development

¾ Second month, teat development starts with rapid

development of mesenchyme tissue surrounding
mammary bud; forces bud to be raised above
surface of epithelium
¾ A slight opening develops in distal end of bud (male
development much slower)
¾ Third month, teat and gland cisterns develop,
invagination of germinal layer which forms a solid
'sprout' (bud undergoes rapid cell division to cause
canalization)
¾ Sprout follows path of least resistance; to teat cistern,
gland cistern and major ducts (lobar)
¾ Cells separate but do not disintegrate
¾ Age about 100 days (embryo 19 cm)

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 Cow : Teat development
¾ As teat grows: tip of mammary bud opens; cells become
cornified similar to epidermis
¾ Gland cistern outlined and layers 2-3 cells thick by 120 days;
continued canalization of gland by sprout
¾ Teat cistern developed at 16 weeks (fetus 30 cm) (3-4 months)
¾ Streak canal is last part to become canalized
¾ At 13 weeks (16 cm) primary sprout reaches maximum and
gives rise to several secondary sprouts from terminal end;
these give rise to duct system
¾ Secondary sprouts then become canalized; development
usually stops here until birth, then tertiary sprouts develop

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 Cow : Support system

a). Fetus (8-12 cm, second month)

mesenchyme cells differentiate into fibrous
tissue: forms threads or bundles of connective
tissue along with development of blood vessels.
b). Connective tissue threads eventually form
whorls to form mammary gland; connective
tissue cells eventually store lipids in cytoplasm.
c). Adipose tissue has increased the size of the
udder halves.
d). Skin and median suspensory ligament are
developed by six months of age (fetal).
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 Cow : Support system

e). Very little further development takes place prior to

birth.
(1). Teats well developed; teat and gland cisterns
present.
(2). Secondary sprouts canalized but sprout end still
exists.
(3). Vascular, lymphatic, connective tissue and four
distinct mammary glands are evident.
(4). Adipose and connective tissue make up the fatty
pads.
(5). Most non-glandular portions are in mature form prior
to birth, but glandular portion is not in mature form.

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 Cow

Normal males develop m teats nor glandular

mammary tissue. Testosterone is responsible
for suppression of mammary gland development
in fetus. Evidence is as follows:
a). Castration of male fetus allows mammary
development.
b). Castration of female fetus also allows
mammary development.
c). Exogenous testosterone inhibits mammary
development in female fetus.

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