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Ovarian Follicular dynamics in
domestic animals
• The Female gamete the oocyte originate and
develop from the ovarian follicles. The ovarian
follicles develop from the primordial germ
cells during fetal period and are called
primordial follicles.
• Follicle is the primary functional unit of ovary
that releases the oocyte and produces the
steroid hormones.
• Gestation
• Embryonic sac endoderm primordial germ cells
– germ cell cords migrate
Epithelial cells Gondal Ridge
•
• Condense around
• germ cells Mitosis
Meiosis
Arrested at prophase -I
Primordial follicles.
Fate of follicles and oocytes.
Total number of follicles
At birth 100,000
12 months 75,000
4-6 years 21,000
Aged cow 2,500
Follicles grow to tertiary characteristic and degenerate.
Maximum number of oocytes ovulated for a cow
10 cycles/year x 12 year = 120 oocytes ovulated/lifespan
100 Days of Gestation
2.9 million
It has been estimated that no more than about 300 oocytes are ever likely to
reach the ovulatory stage during the normal reproductive lifespan of the cow.
• Follicular growth can be classified into three
phases according to their developmental stage
and gonadotropin dependence : (1) follicular
growth through primordial, primary, and
secondary stages gonadotropin-independent
phase), (2) transition from preantral to early
antral stage (gonadotropin-responsive phase),
and (3) continual growth beyond the early
antral stage (gonadotropin-dependent phase),
which includes follicle recruitment, selection,
and ovulation.
• Ovaries of cattle contain two different pools of
follicles, the non-growing pool and the
growing pool. The non-growing pool contains
the primordial follicles, whereas the growing
pool contains the primary, secondary and
tertiary follicles. Entry of primordial follicles
into the growth phase occurs throughout the
reproductive life. The primordial follicles
continuously leave the arrested pool and
undergo the primordial to primary follicle
transition.
After the preovulatory LH surge in the early hours of estrus in the cow,
the follicle is known as the preovulatory follicle.
• The growth of follicles from the primordial to
ovulatory follicles is complex and requires a
couple of days to months.
• The sequence of events involves the growth of
primordial follicles into preantral and then antral
follicles (follicles with a central fluid filled cavity-
the antrum). This transformation involves the
proliferation of granulosa cells and reorganization
of cells forming the follicle.
• The growth of the primordial follicles is
resumed at puberty subsequent to which the
follicles grow in a cyclic fashion that is
repeated at defined intervals regularly
throughout the year in non seasonal breeding
species.
• During this transition the oocytes increase in size
and the surrounding squamous pre-granulosa
cells become cuboidal and proliferate to form a
layer of cuboidal cells around the growing oocyte.
The follicle is now called the primary follicle. The
mechanisms responsible for the initiation of
follicular growth during this phase are poorly
understood although some molecules such as
growth factors and gonadotrophins have been
discussed.
Puberty
Primordial follicle activated Primary and Sec follicle
• Preantral Antral follicles
• Early antral Follicle recruitment, selection,
and ovulation-Follicular waves
Gonadotropin-independent phase
Gonadotropin-dependent phase
Gonadotropin-dependent phase
Mucopolysaccharide
layer Zona pellucida
Tertiary follicles also
called small antral
follicles
Antral Follicle
Granulosa
Theca Internal
It is now known that the antral follicles
are selected to grow and this growth
occurs in a wave like fashion in most
domestic mammalian species. The
follicular growth waves lead to growth in
the size and fluid secretions within the
follicle, expression of estrus, and
ovulation with release of mature oocyte.
• Normally three to six follicles with a diameter
of 4 to 5 mm occur after recruitment of follicle
into a follicular wave.
• From the cohort of the growing follicles one
follicle is selected for continued growth and
becomes dominant. If luteolysis occurs during
the growth phase of the dominant follicles,
final maturation and ovulation occurs. If
luteolysis does not occur during the growing
and maintenance phase of follicles, the fate is
atresia
• Follicle recruitment
• The concept recruitment is used for the entrance
of follicles in the growing pool, but also for the
processes associated with the entrance of
follicles in a wave like growth. FSH appears to
be the key hormone for the initiation of the
follicular wave. The surges in FSH precede the
emergence of a wave. The FSH surges begin 2-
4 days before the detectable (ultrasound)
emergence of a follicular wave (follicles of 4
and 5 mm), peaked 1 or 2 days and started
declining nearly when the follicles of a wave
begin to diverge into a dominant follicle and
subordinate follicles (follicles 6 to 8 mm).
• Recruitment of the cohort containing the
future preovulatory follicle occurs during a
recruitment window which lasts 1, 2 or 3 days
in sheep, cattle or horses respectively. Only
gonadotrophin dependent healthy follicles
are recruited. The number of recruited
follicles growing in the cohort appears to be
highly variable between species. It ranges
from over 50 in pigs, to 5 to 10 in cattle and
1 to 4 in horses. All follicles of the cohort are
capable of ovulating, since selective ablation
of all except one will not postpone ovulation
in sheep and cattle.
• Selection
• Selection means that the number of
growing follicles is brought into line with the
species-specific ovulation number. After
recruitment fewer and fewer recruited
follicles continue in growth and one follicle
is selected to become dominant while the
remaining members of the recruited
follicles become static and eventually
undergo atresia via apoptosis.
• Dominance
• Follicles are functionally dominant (capable of
ovulating after luteal regression) while they are still
growing. Follicles acquired ovulatory capacity at
about 10 mm, corresponding to about 1 day after the
start of follicular deviation.
• Dominance negative feedback effects of products of
the dominant follicle on circulating FSH.
• Dominance progressive increases in the ability of
theca cells to produce androgen and granulosa cells
to aromatize androgen to estradiol.
• Dominant follicles grow to a much larger size (from
8.5 mm at the end of selection to 12-20 mm) in 3 to 4
days.
• Dominant follicle . Progesterone LH Ovulation
• Dominant follicle No follicular wave
Gonadotropin
Independent
FSH
Recruitment
Initial Follicular Growth
Small Antral
Follicle
50 - 60 days
Follicular Waves in Cattle
Ovulation
Ovulation
FollicularSize
Day After Ovulation
9 16 21
FSH Sensitive Pool
Recruitment
Selection
Dominance
Atresia
Progesterone
Follicular Waves in Cattle
Ovulation
FollicularSize
Day After Ovulation
9 16 21
Recruitment FSH estradiol (-)
Selection FSH estradiol (-)
inhibin (-)
Dominance FSH estradiol (-)
inhibin (-)
Atresia
estradiol
inhibin
Progesterone
Three Follicular Waves in Cattle
Ovulation
FollicularSize
Day After Ovulation
9 16 21
Progesterone
Dominance
Recruitment
Selection
Ovulation
FSH, E2
FSH, E2
inhibin, LH
FSH, E2
inhibin, LH
Two Follicular Waves
10Ovulation 21
FollicularSize
Recruitment
Selection
Dominance
Atresia Ovulation
Day After Ovulation
Species Variation in Follicular Waves
• Cattle - 2 or 3 / cycle
• Sheep - 4 or 5 / cycle
• Pigs - 1 / cycle
• Horses - 1 / cycle
Cl-progesterone
Cl-progesterone, inhibin
Theca Interna
Granulosa
Receptor
LH
cAMP
Cholesterol
Testosterone
PKA
Receptor
FSH
Testosterone
cAMP
Receptor
LH
Selection
Dominant Follicle
Express LH Receptor
cAMP
Estradiol
PKA
Preovulatory LH Surge
Ovulation
Increased Blood
Flow to Ovary and
Follicle
Vascular
Permeability
Plasminogen
Cumulus
Expansion
Oocyte
Separates
From
Follicular
Wall
Contraction
of Smooth
Muscle
Collagenase (inactive)
Follicular Wall
Weakens
Plasmin
Collagenase (active)
Protein Synthesis
in and around Follicle
Plasminogen
Activator
Progesterone Prostaglandin
Synthesis
PGE and PGF
Follicular dynamics in buffaloes
Buffaloes evidence 1-, 2- or 3- wave cycles with
the 2-wave cycle being the most common pattern
of follicular growth Size of ovulatory follicle above
8.5mm
In some breeds one wave cycle is common for
example the Surti breed
During hot summer months there is variable degree of
ovarian follicular turnover in one or both ovaries
without expression of estrus signs and regression of
dominant follicles instead of their ovulation.
The types of follicular waves that develop in mares are
major waves (characterized by dominant and subordinate
follicles) and minor waves (largest follicle does not attain
the diameter of a dominant follicle).
Follicular dynamics in mares
In the mare ovary there are approximately
40,000 primordial follicles and 100 growing follicles
Atresia (regression) of follicles is rare until
they reach 1 mm
In some breeds (e.g. Quarter-Horses, Ponies), usually only
one major wave develops in late diestrus and culminates in the
estrous ovulation. In other breeds (e.g. Thoroughbreds), a
secondary major wave frequently develops in early diestrus,
and the dominant follicle may be anovulatory (more common),
or occasionally ovulatory (diestrous ovulation).
Minor follicular waves have been demonstrated in mares in
variable patterns. In all horse breeds, however, a major
ovulatory wave begins at mid-cycle and one follicle
(occasionally two, rarely three) becomes dominant and
ovulates.
• The ovulatory waves, as well as major
anovulatory waves and minor waves,
originate from the stimulation of an FSH
surge, which reaches a peak when the
largest follicle is about 13 mm.
• The physiologically selected dominant
follicle grows to a large diameter (≥ 28
mm) and then either regresses
(anovulatory major wave) or ovulates
(ovulatory wave).
• Maximum diameter of the dominant follicle is
smaller for major anovulatory waves than for
ovulatory waves (e.g., means of 37 and 46
mm
• A paradox in mares is the occurrence of
ovulation from the dominant follicle of what
was expected to be an anovulatory wave.
These ovulations have been called
secondary or diestrus ovulations and occur
during high progesterone concentrations.
Follicular dynamics in sheep
• In sheep follicles ≥5mm in diameter would
exhibit a wave-like pattern while follicles
smaller than 4mm would grow randomly. Both
patterns of growth are classified as primary
and secondary follicular waves, respectively.
• Two to 3 follicular waves per cycle are
common in sheep, and 3 or 4 follicular waves
per cycle are most common in goats
• During estrous cycles, the dominant and
largest subordinate follicles reach maximum
diameters of 5 to 7 mm and 3 to 5 mm
respectively in sheep. In most cases the
ovulatory follicles develop from the cohort of
follicles from the last follicular wave. However,
the ovulatory follicles can also derive from the
penultimate follicular wave with the result
that follicles can ovulate both from the last
and the second last follicular waves of the
cycle.
Follicular dynamics in goats
• In goats on any one day of the estrous cycle
there are 5 to 10 follicles > 3 mm in diameter
in the ovaries and follicles ovulate at or
between 6 and 9 mm in diameter. As in sheep
double ovulations can derive from follicles of
the last and the second last wave.
• The above lectures are also explained in video
lectures at my YouTube Channel Govind
Narayan Purohit
• Kindly share the videos and subscribe to my
channel if you like them
• Thanks

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Lecture 5 follicular dynamics in domestic animals

  • 1. Ovarian Follicular dynamics in domestic animals • The Female gamete the oocyte originate and develop from the ovarian follicles. The ovarian follicles develop from the primordial germ cells during fetal period and are called primordial follicles. • Follicle is the primary functional unit of ovary that releases the oocyte and produces the steroid hormones.
  • 2. • Gestation • Embryonic sac endoderm primordial germ cells – germ cell cords migrate Epithelial cells Gondal Ridge • • Condense around • germ cells Mitosis Meiosis Arrested at prophase -I Primordial follicles.
  • 3. Fate of follicles and oocytes. Total number of follicles At birth 100,000 12 months 75,000 4-6 years 21,000 Aged cow 2,500 Follicles grow to tertiary characteristic and degenerate. Maximum number of oocytes ovulated for a cow 10 cycles/year x 12 year = 120 oocytes ovulated/lifespan 100 Days of Gestation 2.9 million It has been estimated that no more than about 300 oocytes are ever likely to reach the ovulatory stage during the normal reproductive lifespan of the cow.
  • 4. • Follicular growth can be classified into three phases according to their developmental stage and gonadotropin dependence : (1) follicular growth through primordial, primary, and secondary stages gonadotropin-independent phase), (2) transition from preantral to early antral stage (gonadotropin-responsive phase), and (3) continual growth beyond the early antral stage (gonadotropin-dependent phase), which includes follicle recruitment, selection, and ovulation.
  • 5. • Ovaries of cattle contain two different pools of follicles, the non-growing pool and the growing pool. The non-growing pool contains the primordial follicles, whereas the growing pool contains the primary, secondary and tertiary follicles. Entry of primordial follicles into the growth phase occurs throughout the reproductive life. The primordial follicles continuously leave the arrested pool and undergo the primordial to primary follicle transition.
  • 6. After the preovulatory LH surge in the early hours of estrus in the cow, the follicle is known as the preovulatory follicle.
  • 7.
  • 8. • The growth of follicles from the primordial to ovulatory follicles is complex and requires a couple of days to months. • The sequence of events involves the growth of primordial follicles into preantral and then antral follicles (follicles with a central fluid filled cavity- the antrum). This transformation involves the proliferation of granulosa cells and reorganization of cells forming the follicle.
  • 9. • The growth of the primordial follicles is resumed at puberty subsequent to which the follicles grow in a cyclic fashion that is repeated at defined intervals regularly throughout the year in non seasonal breeding species.
  • 10. • During this transition the oocytes increase in size and the surrounding squamous pre-granulosa cells become cuboidal and proliferate to form a layer of cuboidal cells around the growing oocyte. The follicle is now called the primary follicle. The mechanisms responsible for the initiation of follicular growth during this phase are poorly understood although some molecules such as growth factors and gonadotrophins have been discussed.
  • 11. Puberty Primordial follicle activated Primary and Sec follicle • Preantral Antral follicles • Early antral Follicle recruitment, selection, and ovulation-Follicular waves Gonadotropin-independent phase Gonadotropin-dependent phase Gonadotropin-dependent phase
  • 12. Mucopolysaccharide layer Zona pellucida Tertiary follicles also called small antral follicles
  • 14. It is now known that the antral follicles are selected to grow and this growth occurs in a wave like fashion in most domestic mammalian species. The follicular growth waves lead to growth in the size and fluid secretions within the follicle, expression of estrus, and ovulation with release of mature oocyte.
  • 15. • Normally three to six follicles with a diameter of 4 to 5 mm occur after recruitment of follicle into a follicular wave. • From the cohort of the growing follicles one follicle is selected for continued growth and becomes dominant. If luteolysis occurs during the growth phase of the dominant follicles, final maturation and ovulation occurs. If luteolysis does not occur during the growing and maintenance phase of follicles, the fate is atresia
  • 16.
  • 17. • Follicle recruitment • The concept recruitment is used for the entrance of follicles in the growing pool, but also for the processes associated with the entrance of follicles in a wave like growth. FSH appears to be the key hormone for the initiation of the follicular wave. The surges in FSH precede the emergence of a wave. The FSH surges begin 2- 4 days before the detectable (ultrasound) emergence of a follicular wave (follicles of 4 and 5 mm), peaked 1 or 2 days and started declining nearly when the follicles of a wave begin to diverge into a dominant follicle and subordinate follicles (follicles 6 to 8 mm).
  • 18. • Recruitment of the cohort containing the future preovulatory follicle occurs during a recruitment window which lasts 1, 2 or 3 days in sheep, cattle or horses respectively. Only gonadotrophin dependent healthy follicles are recruited. The number of recruited follicles growing in the cohort appears to be highly variable between species. It ranges from over 50 in pigs, to 5 to 10 in cattle and 1 to 4 in horses. All follicles of the cohort are capable of ovulating, since selective ablation of all except one will not postpone ovulation in sheep and cattle.
  • 19. • Selection • Selection means that the number of growing follicles is brought into line with the species-specific ovulation number. After recruitment fewer and fewer recruited follicles continue in growth and one follicle is selected to become dominant while the remaining members of the recruited follicles become static and eventually undergo atresia via apoptosis.
  • 20. • Dominance • Follicles are functionally dominant (capable of ovulating after luteal regression) while they are still growing. Follicles acquired ovulatory capacity at about 10 mm, corresponding to about 1 day after the start of follicular deviation. • Dominance negative feedback effects of products of the dominant follicle on circulating FSH. • Dominance progressive increases in the ability of theca cells to produce androgen and granulosa cells to aromatize androgen to estradiol. • Dominant follicles grow to a much larger size (from 8.5 mm at the end of selection to 12-20 mm) in 3 to 4 days. • Dominant follicle . Progesterone LH Ovulation • Dominant follicle No follicular wave
  • 22. Follicular Waves in Cattle Ovulation Ovulation FollicularSize Day After Ovulation 9 16 21 FSH Sensitive Pool Recruitment Selection Dominance Atresia Progesterone
  • 23. Follicular Waves in Cattle Ovulation FollicularSize Day After Ovulation 9 16 21 Recruitment FSH estradiol (-) Selection FSH estradiol (-) inhibin (-) Dominance FSH estradiol (-) inhibin (-) Atresia estradiol inhibin Progesterone
  • 24. Three Follicular Waves in Cattle Ovulation FollicularSize Day After Ovulation 9 16 21 Progesterone Dominance Recruitment Selection Ovulation FSH, E2 FSH, E2 inhibin, LH FSH, E2 inhibin, LH
  • 25. Two Follicular Waves 10Ovulation 21 FollicularSize Recruitment Selection Dominance Atresia Ovulation Day After Ovulation
  • 26. Species Variation in Follicular Waves • Cattle - 2 or 3 / cycle • Sheep - 4 or 5 / cycle • Pigs - 1 / cycle • Horses - 1 / cycle Cl-progesterone Cl-progesterone, inhibin
  • 28. Preovulatory LH Surge Ovulation Increased Blood Flow to Ovary and Follicle Vascular Permeability Plasminogen Cumulus Expansion Oocyte Separates From Follicular Wall Contraction of Smooth Muscle Collagenase (inactive) Follicular Wall Weakens Plasmin Collagenase (active) Protein Synthesis in and around Follicle Plasminogen Activator Progesterone Prostaglandin Synthesis PGE and PGF
  • 29. Follicular dynamics in buffaloes Buffaloes evidence 1-, 2- or 3- wave cycles with the 2-wave cycle being the most common pattern of follicular growth Size of ovulatory follicle above 8.5mm In some breeds one wave cycle is common for example the Surti breed During hot summer months there is variable degree of ovarian follicular turnover in one or both ovaries without expression of estrus signs and regression of dominant follicles instead of their ovulation.
  • 30. The types of follicular waves that develop in mares are major waves (characterized by dominant and subordinate follicles) and minor waves (largest follicle does not attain the diameter of a dominant follicle). Follicular dynamics in mares In the mare ovary there are approximately 40,000 primordial follicles and 100 growing follicles Atresia (regression) of follicles is rare until they reach 1 mm
  • 31. In some breeds (e.g. Quarter-Horses, Ponies), usually only one major wave develops in late diestrus and culminates in the estrous ovulation. In other breeds (e.g. Thoroughbreds), a secondary major wave frequently develops in early diestrus, and the dominant follicle may be anovulatory (more common), or occasionally ovulatory (diestrous ovulation). Minor follicular waves have been demonstrated in mares in variable patterns. In all horse breeds, however, a major ovulatory wave begins at mid-cycle and one follicle (occasionally two, rarely three) becomes dominant and ovulates.
  • 32. • The ovulatory waves, as well as major anovulatory waves and minor waves, originate from the stimulation of an FSH surge, which reaches a peak when the largest follicle is about 13 mm. • The physiologically selected dominant follicle grows to a large diameter (≥ 28 mm) and then either regresses (anovulatory major wave) or ovulates (ovulatory wave).
  • 33. • Maximum diameter of the dominant follicle is smaller for major anovulatory waves than for ovulatory waves (e.g., means of 37 and 46 mm • A paradox in mares is the occurrence of ovulation from the dominant follicle of what was expected to be an anovulatory wave. These ovulations have been called secondary or diestrus ovulations and occur during high progesterone concentrations.
  • 34. Follicular dynamics in sheep • In sheep follicles ≥5mm in diameter would exhibit a wave-like pattern while follicles smaller than 4mm would grow randomly. Both patterns of growth are classified as primary and secondary follicular waves, respectively. • Two to 3 follicular waves per cycle are common in sheep, and 3 or 4 follicular waves per cycle are most common in goats
  • 35. • During estrous cycles, the dominant and largest subordinate follicles reach maximum diameters of 5 to 7 mm and 3 to 5 mm respectively in sheep. In most cases the ovulatory follicles develop from the cohort of follicles from the last follicular wave. However, the ovulatory follicles can also derive from the penultimate follicular wave with the result that follicles can ovulate both from the last and the second last follicular waves of the cycle.
  • 36. Follicular dynamics in goats • In goats on any one day of the estrous cycle there are 5 to 10 follicles > 3 mm in diameter in the ovaries and follicles ovulate at or between 6 and 9 mm in diameter. As in sheep double ovulations can derive from follicles of the last and the second last wave.
  • 37. • The above lectures are also explained in video lectures at my YouTube Channel Govind Narayan Purohit • Kindly share the videos and subscribe to my channel if you like them • Thanks