Animal Science 434

Animal Science 434

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)