Animal Science 434

The Follicular Phase of the Estrous Cycle

Tonic and Preovulatory Surge of GnRHPreovulatory GnRH

SurgeTonic GnRH Release

GnRH

(pg

/ml)

GnRH

(pg

/ml)

Hours

Hours

Hypothalamus

GnRH

AnteriorPituitary

CL FollicleOvary

LH, FSH

LH LH, FSH

Inhibin (-)

EstradiolProgesterone

Estradiol

(-)(-)

Tonic and Preovulatory Surge of GnRHPreovulatory GnRH

SurgeTonic GnRH Release

GnRH

(pg

/ml)

GnRH

(pg

/ml)

Hours

Hours

The Follicular Phase

Hypothalamus

GnRH

AnteriorPituitary

FollicleOvary

LH, FSH

LH, FSH

Inhibin (-)Estradiol

Estradiol (-)

LH

Progesterone(-)

CL

Start of Follicular Phase

Estradiol (-)Hypothalamus

GnRH

AnteriorPituitary

FollicleOvary

LH, FSH

LH, FSH

Inhibin (-)Estradiol

CL Regression

Estradiol (+)Hypothalamus

GnRH

AnteriorPituitary

FollicleOvary

LH, FSH

LH, FSH

Inhibin (-)Estradiol

Ends in LH surge and ovulation

The Follicular Phase

Tertiary

FollicularProgression

Primordial

Primary

Secondary

Growth and Atresia of Follicles

Atresia

At birth 100,000 12 months 75,0004-6 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

Superovulation or Ovum Pick-up (OPU) - rescue some follicles from atresia

100 Days of Gestation 2.9

million

GonadotropinIndependent

Initial Follicular Growth

Small AntralFollicle

50 - 60 days

FSH

Recruitment

Follicular Waves in Cattle

Ovulation

Folli

cula

r Siz

e

Day9 16 21

Ovulation

FSH Sensitive Pool

Recruitment

Selection

Dominance

Atresia

Ovulation

Ovulation

Folli

cula

r Siz

e

9 16 21

FSH Sensitive Pool

Recruitment

Selection

Dominance

Atresia Progesterone

Day

Ovulation

Folli

cula

r Siz

e

9 16 21

Recruitment FSH estradiol (-)

Selection FSH estradiol (-)inhibin (-)

Dominance FSH estradiol (-)inhibin (-)

Atresia estradiolinhibin

Progesterone FSH

Day Ovulation

Folli

cula

r Siz

e

9 16 21

Recruitment

Selection

Dominance

Atresia

Progesterone

Day

Ovulation

Folli

cula

r Siz

e

9 16 21

Progesterone

Day Ovulation

Folli

cula

r Siz

e

9 16 21

Progesterone

Day

Ovulation

Folli

cula

r Siz

e

9 16 21

Dominance

Recruitment

Selection

OvulationProgesterone

Day

Two Follicular Waves

10Ovulation 21

Folli

cula

r Siz

e

Recruitment

Selection

Dominance Atresia Ovulation

Progesterone

Day

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

If first wave stops/fails, then a

second wave emerges!!!

Gonadotropin Action Within

the Follicle

Antral Follicle

Granulosa

Theca Internal

Theca Interna

Granulosa

Receptor

LH

cAMPCholesterol

TestosteronePKA Receptor

FSH

Test.cAMP

EstradiolPKA

Receptor

LH

cAMPCholesterol

TestosteronePKA Receptor

FSH

Test.

cAMP

EstradiolPKA

cAMP

Receptor

LH

SelectionDom. Foll.

Express LH Receptor

Theca Interna

Granulosa

Ovulation

Tunica Albuginea

Germinal Epithelium

Theca Externa

Theca Interna

GranulosaBasement Membrane

• protein synthesis• steroid synthesis• prostaglandin synthesis• plasminogen activator

synthesis

Blocking of these events in the follicle prevents ovulation.

Preovulatory LH Surge

Ovulation

CumulusExpansion

OocyteSeparates

FromFollicular

Wall

Cumulus Expansion

Unexpanded Expanded

Hyaluronic Acid and Protein Production

Cumulus and OocyteSeparation Protein synthesis changes

in and around Follicle

PlasminogenActivator

Progesterone Prostaglandin Synthesis

PGE and PGF

Preovulatory LH Surge

Ovulation

CumulusExpansion

OocyteSeparates

FromFollicular

Wall

Preovulatory LH Surge

Ovulation

CumulusExpansion

OocyteSeparates

FromFollicular

Wall

Protein synthesis changesin and around Follicle

PlasminogenActivator

Progesterone Prostaglandin Synthesis

PGE and PGF

Increased BloodFlow to Ovary and

Follicle

Vascular Permeability

Plasminogen

Histamine, PGE2

Foll. pressure

Edema

Preovulatory LH Surge

Ovulation

CumulusExpansion

OocyteSeparates

FromFollicular

Wall

Protein synthesis changesin and around Follicle

PlasminogenActivator

Progesterone Prostaglandin Synthesis

PGE and PGF

Increased BloodFlow to Ovary and

Follicle

Vascular Permeability

Plasminogen

Histamine, PGE2

Foll. pressure

Edema

Collagen. (inact.)

Follicular Wall Weakens

Plasmin

Collagenase (act.)

Preovulatory LH Surge

Ovulation

CumulusExpansion

OocyteSeparates

FromFollicular

WallContractionSm. Muscle

Collagen. (inact.)

Follicular Wall Weakens

Plasmin

Collagenase (act.)

Protein synthesis changesin and around Follicle

PlasminogenActivator

Progesterone Prostaglandin Synthesis

PGE and PGF

Increased BloodFlow to Ovary and

Follicle

Vascular Permeability

Plasminogen

Histamine, PGE2

Foll. pressure

Edema

Types of Ovulators

Spontaneous Ovulators

Induced Ovulators

Sensory NeuronsNerve endings sensing copulation

PenisCopulation

Induced Ovulators

GnRHBloo

d LH

Time (hr)LH

Spinal Chord

Anterior Pit.

Posterior Pit.

Hypothalamus

Stimulation

Sensory NeuronsNerve endings

sensing copulation

PenisCopulation

Induced Ovulators

LH

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 OocyteMeiosisInterphase DNA synthesis Meiotic prophase

Move to germinal ridgeMitotic divisions

Prophase of MeiosisLeptotene, ZygotenePacytene, DiploteneDictyotene

Meiotic Arrest

Follicle Cells

Growth

zona pellucida formationmRNA productionProtein synthesisCortical granule formation

nuclear maturationcytoplasmic maturation

GonadotropinIndependent

GonadotropinDependent

Remains primary oocyte until LH surge

Oogonia in Egg Nest

Fetal Pig Ovary

Primary Oocytes

OogoniaPrimary

Oocytes in Primordial Follicles

Primary Oocyte in Primary Follicle

Fetal Oocyte DevelopmentFertilization Birth

Mitosis Meiosis

Mouse

19 d

Sow

114 d

Cow

280 d

Ovulation of Tertiary FollicleFormation of the Zona Pellucida

Corona Radiata

Zona PellucidaOocyte

Corona Radiata Zona Pellucida Oocyte

Gap Junctions

• OMI - Oocyte Maturation Inhibitor

• MPF - Maturation promoting factor

• GV - germinal vesicle(nucleus)

During Oocyte Growth and Before the LH Surge

Gap Junctions Allow Cell to Cell Communication!

pre-MPF MPF

GV

OMI

cAMP

cAMP

PKA

The LH Surge

Gap Junctions are Destroyed!

GV

GVBD Resumptionof Meiosis

pre-MPF MPF

cAMP

PKA

The LH Surge

Gap Junctions are Destroyed!

LH Surge Resumption of Meiosis

First polar body emitted, arrest at metaphase II

OvulationPrimary Oocyte Secondary

Oocyte

Sperm PenetrationZygote

(pronucleate egg)

4N 4N 2N

2NN N

(mostspecies)

LH Surge Resumption of Meiosis

First polar body emitted, arrest at metaphase II

OvulationPrimary Oocyte Secondary

Oocyte

Sperm Penetration

4N 4N 2N

2NN N

(mostspecies)Ovulation

•Dog, Fox

Sperm Pen.•Dog, Fox

Zygote (pronucleate egg)