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Animal Science 434
Lecture 11: The Follicular Phase of the Estrous Cycle
Tonic and Preovulatory Surge of GnRH
HypothalamusHypothalamus
GnRH
AnteriorPituitary
AnteriorPituitary
CL FollicleOvary
LH, FSH
LH LH, FSH
Inhibin (-)
EstradiolEstradiolProgesteroneProgesterone
Estradiol
(-)(-)
Tonic and Preovulatory Surge of GnRH
AtresiaCLCAOvulationCLDays Relative to the Gonadotropin Surge012345678-1- 2- 3- 4- 5- 6-7LHFSHPGF2αEstradiolProgesteroneMetestrusDiestrusProestrusDiestrusEstrus
Follicular Phase
HypothalamusHypothalamus
GnRH
AnteriorPituitary
AnteriorPituitary
FollicleOvary
LH, FSH
LH, FSH
Inhibin (-)Estradiol
EstradiolEstradiol (-)
LH
ProgesteroneProgesterone
(-)
CL
EstradiolEstradiol (+)
HypothalamusHypothalamus
GnRH
AnteriorPituitary
AnteriorPituitary
FollicleOvary
LH, FSH
LH, FSH
Inhibin (-)Estradiol
AtresiaCLCAOvulationCLDays Relative to the Gonadotropin Surge012345678-1- 2- 3- 4- 5- 6-7LHFSHPGF2αEstradiolProgesteroneMetestrusDiestrusProestrusDiestrusEstrus
Follicular Phase
Follicular Progression
Primordial Primar
ySecondary
Tertiary
Growth and Atresia of Follicles
Atresia
Total # of follicles
At birth 100,000
12 months 75,000
4-6 years 21,000
Aged cow 2,500
Follicles undergo atresia at all stages of development.
Maximum number of oocytes ovulated for a cow
17 cycles/year x 8 year = 136 oocytes ovulated / lifespan
Fate of follicles and oocytes
100 Days of Gestation 2.9 million100 Days of Gestation 2.9 million
Superovulation; rescue follicles from undergoing atresiawith FSH treatment.Superovulation; rescue follicles from undergoing atresiawith FSH treatment.
Total # of follicles
At birth 100,000
12 months 75,000
4-6 years 21,000
Aged cow 2,500
Follicles undergo atresia at all stages of development.
Maximum number of oocytes ovulated for a cow
17 cycles/year x 8 year = 136 oocytes ovulated / lifespan
Fate of follicles and oocytes
GonadotropinIndependent
FSH
RecruitmentRecruitment
Initial Follicular Growth
Small AntralFollicle
50 - 60 days
Follicular Waves in CattleFollicular Waves in Cattle
OvulationOvulation
Ovulation
Fo
llicu
lar
Siz
e
Day After Ovulation9 16 21
FSH Sensitive Pool
RecruitmentRecruitment
SelectionSelection
DominanceDominance
Atresia
Follicular Waves in CattleFollicular Waves in Cattle
OvulationOvulation
Ovulation
Fo
llicu
lar
Siz
e
Day After Ovulation9 16 21
FSH Sensitive Pool
RecruitmentRecruitment
SelectionSelection
DominanceDominance
Atresia
Progesterone
Follicular Waves in CattleFollicular Waves in Cattle
Ovulation
Fo
llicu
lar
Siz
e
Day After Ovulation9 16 21
RecruitmentRecruitment
FSH estradiol (-)
SelectionSelection FSH estradiol (-) inhibin (-)
DominanceDominance FSH estradiol (-) inhibin (-)
Atresia
estradiolinhibin
Progesterone FSH
Follicular Waves in CattleFollicular Waves in Cattle
Ovulation
Fo
llicu
lar
Siz
e
Day After Ovulation9 16 21
RecruitmentRecruitment
SelectionSelection
DominanceDominance
Atresia
Progesterone
Follicular Waves in CattleFollicular Waves in Cattle
Ovulation
Fo
llicu
lar
Siz
e
Day After Ovulation9 16 21
Progesterone
Follicular Waves in CattleFollicular Waves in Cattle
Ovulation
Fo
llicu
lar
Siz
e
Day After Ovulation9 16 21
Progesterone
Follicular Waves in CattleFollicular Waves in Cattle
Ovulation
Fo
llicu
lar
Siz
e
Day After Ovulation9 16 21
Progesterone
DominanceDominance
RecruitmentRecruitment
SelectionSelection
OvulationOvulation
Two Follicular WavesTwo Follicular Waves
10Ovulation 21
Fo
llicu
lar
Siz
e
RecruitmentRecruitment
SelectionSelection
DominanceDominanceAtresia OvulationOvulation
Day After Ovulation
Progesterone
Follicular Wave Emergence
• Recruitment = Emergence
• FSH always controls emergence
• Increase in FSH precedes emergence
Species Variation in Follicular Waves
• Cattle - 2 or 3 / cycle
• Sheep - 4 or 5 / cycle
• Pigs - 1 / cycle
• Horses - 1 / cycle
• Human - 1 / cycle
Cl-progesterone
Cl-progesterone, inhibin
Gonadotropin Action Within
the Follicle
Antral Follicle
Granulosa
Theca Internal
Theca InternaTheca Interna
GranulosaGranulosa
Blo
od
Receptor
LH
cAMP
Cholesterol
Testosterone
PKA
Receptor
FSH
Testosterone
cAMP
Estradiol
PKA
Theca InternaTheca Interna
GranulosaGranulosa
Blo
od
Receptor
LH
cAMP
Cholesterol
Testosterone
PKA
Receptor
FSH
TestosteronecAMP
Receptor
LH
Selection
Dominant FollicleExpress LH Receptor
cAMP
Estradiol
PKA
Ovulation
Tunica Albuginea
Germinal Epithelium
Theca Externa
Theca Interna
Granulosa
Basement Membrane
• protein synthesis
• steroid synthesis
• prostaglandin synthesis
• plasminogen activator synthesis
Blocking of these events in the follicle prevents ovulation.
Preovulatory LH Surge
Ovulation
CumulusExpansionCumulus
Expansion
OocyteSeparates
FromFollicular
Wall
OocyteSeparates
FromFollicular
Wall
Cumulus ExpansionCumulus Expansion
UnexpandedUnexpanded ExpandedExpanded
Hyaluronic Acid and Protein Production
Cumulus and OocyteSeparation
Preovulatory LH Surge
Ovulation
CumulusExpansionCumulus
Expansion
OocyteSeparates
FromFollicular
Wall
OocyteSeparates
FromFollicular
Wall
Protein synthesis changesin and around Follicle
Protein synthesis changesin and around Follicle
PlasminogenActivator
PlasminogenActivator
ProgesteroneProgesterone Prostaglandin Synthesis
PGE and PGF
Prostaglandin Synthesis
PGE and PGF
Preovulatory LH Surge
Ovulation
Increased BloodFlow to Ovary and
Follicle
Increased BloodFlow to Ovary and
Follicle
Vascular Permeability
Vascular Permeability
PlasminogenPlasminogen
CumulusExpansionCumulus
Expansion
OocyteSeparates
FromFollicular
Wall
OocyteSeparates
FromFollicular
Wall
Protein synthesis changesin and around Follicle
Protein synthesis changesin and around Follicle
PlasminogenActivator
PlasminogenActivator
ProgesteroneProgesterone Prostaglandin Synthesis
PGE and PGF
Prostaglandin Synthesis
PGE and PGF
HistaminePGE2
HistaminePGE2
FollicularpressureFollicularpressure
EdemaEdema
Preovulatory LH Surge
Ovulation
Increased BloodFlow to Ovary and
Follicle
Increased BloodFlow to Ovary and
Follicle
Vascular Permeability
Vascular Permeability
PlasminogenPlasminogen
CumulusExpansionCumulus
Expansion
OocyteSeparates
FromFollicular
Wall
OocyteSeparates
FromFollicular
Wall
Collagenase (inactive)Collagenase (inactive)
Follicular WallWeakens
Follicular WallWeakens
PlasminPlasmin
Collagenase (active)Collagenase (active)
Protein synthesis changesin and around Follicle
Protein synthesis changesin and around Follicle
PlasminogenActivator
PlasminogenActivator
ProgesteroneProgesterone Prostaglandin Synthesis
PGE and PGF
Prostaglandin Synthesis
PGE and PGF
HistaminePGE2
HistaminePGE2
FollicularpressureFollicularpressure
EdemaEdema
Preovulatory LH Surge
Ovulation
Increased BloodFlow to Ovary and
Follicle
Increased BloodFlow to Ovary and
Follicle
Vascular Permeability
Vascular Permeability
PlasminogenPlasminogen
CumulusExpansionCumulus
Expansion
OocyteSeparates
FromFollicular
Wall
OocyteSeparates
FromFollicular
Wall
Contractionof Smooth
Muscle
Contractionof Smooth
Muscle
Collagenase (inactive)Collagenase (inactive)
Follicular WallWeakens
Follicular WallWeakens
PlasminPlasmin
Collagenase (active)Collagenase (active)
Protein synthesis changesin and around Follicle
Protein synthesis changesin and around Follicle
PlasminogenActivator
PlasminogenActivator
ProgesteroneProgesterone Prostaglandin Synthesis
PGE and PGF
Prostaglandin Synthesis
PGE and PGF
HistaminePGE2
HistaminePGE2
FollicularpressureFollicularpressure
EdemaEdema
Types of OvulatorsTypes of Ovulators
Spontaneous Ovulators
Spontaneous Ovulators
Induced OvulatorsInduced
Ovulators
Sensory NeuronsSensory NeuronsNerve
endings sensing
copulation
PenisPenisCopulationCopulation
Induced Ovulators
GnRHGnRH
BloodLH
Time (hr)
LHLH
Spinal Chord
Anterior Pit.
Posterior Pit.
Hypothalamus
StimulationStimulation
Sensory NeuronsSensory NeuronsNerve
endings sensing
copulation
PenisPenisCopulationCopulation
LHLH
Cats• Induced Ovulators• Single copulation– Only works 50% of the time
• Multiple copulations– Higher LH surge
Spontaneous Ovulators
• Retain some neural control of ovulation– heifers can alter the timing of the LH
surge by clitoral stimulation– human rape cases result in higher than
expected pregnancy rates
OogenesisPrimordial Germ Cells
Oogonia
Primary Oocyte
Growth
Initiation of MeiosisInterphase DNA synthesis Meiotic prophase begins
zona pellucida formationmRNA productionprotein synthesiscortical granule formation
nuclear maturationcytoplasmic maturation
Migration to germinal ridgeMitotic divisions
Prophase of Meiosisleptotenezygotenepachytenediplotene
Meiotic Arrestdictyotene
GonadotropinIndependent
GonadotropinDependent
Follicle Cells
Oogonia in Egg Nest
Fetal Pig Ovary
Oogonia and Primary Oocytes
Primary Oocytes in Primordial Follicles
Primary Oocyte in Primary Follicle
Fetal Oocyte Development
FertilizationFertilization BirthBirthMitosis Meiosis
Mouse
19 d19 d
Sow
114 d114 d
Cow
280 d280 d
Ovulation of Tertiary Follicle
Formation of the Zona PellucidaCorona RadiataCorona Radiata
Zona PellucidaZona Pellucida
OocyteOocyte
Corona RadiataCorona Radiata Zona PellucidaZona Pellucida OocyteOocyte
Gap Junctions
• OMI - Oocyte Maturation Inhibitor
• MPF - Maturation promoting factor
• GV - germinal vesicle (nucleus)
pre-MPF MPF
GV
During Oocyte Growth and Before the LH Surge
OMI
cAMP
Gap Junctions Allow Cell to Cell Communication!Gap Junctions Allow Cell to Cell Communication!
cAMP
PKA
The LH Surge
Gap Junctions are Destroyed!Gap Junctions are Destroyed!
GV
GVBD
The LH Surge
Resumptionof Meiosis
Gap Junctions are Destroyed!Gap Junctions are Destroyed!
pre-MPF MPF
cAMP
PKA
LH Surge Resumption of Meiosis
First polar bodyemitted, arrest at
metaphase II of meiosis
Ovulation
Primary OocyteSecondary
Oocyte
SpermPenetration
Zygote (pronucleate egg)
4N 4N 2N
2NN N
(most species)(most species)
LH Surge Resumption of Meiosis
First polar bodyemitted, arrest at
metaphase II of meiosis
Ovulation
Primary OocyteSecondary
Oocyte
SpermPenetration
Zygote (pronucleate egg)
4N 4N 2N
2NN N
Ovulation• Dog• Fox
Ovulation• Dog• Fox
Sperm Penetration• Dog• Fox
Sperm Penetration• Dog• Fox (most species)(most species)