tonic and preovulatory surge of gnrh · tonic gnrh release (pg) (pg) hours hours hypothalamus gnrh...
TRANSCRIPT
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)