Lecture 11: The Follicular Phase of the Estrous Cycle Animal Science 434 Lecture 11: The Follicular Phase of the Estrous Cycle

Tonic and Preovulatory Surge of GnRH

Hypothalamus Progesterone Estradiol (-) (-) GnRH Anterior Pituitary Inhibin (-) LH, FSH Estradiol LH, FSH LH CL Follicle Ovary

Tonic and Preovulatory Surge of GnRH

Follicular Phase

Hypothalamus LH Progesterone (-) CL Estradiol (-) GnRH Anterior Pituitary Inhibin (-) LH, FSH Estradiol LH, FSH Follicle Ovary

Hypothalamus Estradiol (+) GnRH Anterior Pituitary Inhibin (-) LH, FSH Estradiol LH, FSH Follicle Ovary

Follicular Phase

Follicular Progression Secondary Primary Primordial Tertiary

Growth and Atresia of Follicles

Fate of follicles and oocytes 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 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 100 Days of Gestation 2.9 million Superovulation; rescue follicles from undergoing atresia with FSH treatment.

Initial Follicular Growth Small Antral Follicle 50 - 60 days Gonadotropin Independent FSH Recruitment

Follicular Waves in Cattle Atresia Follicular Size Recruitment Dominance Ovulation Selection FSH Sensitive Pool Ovulation 9 16 21 Day After Ovulation

Follicular Waves in Cattle Progesterone Atresia Follicular Size Recruitment Dominance Ovulation Selection FSH Sensitive Pool Ovulation 9 16 21 Day After Ovulation

Follicular Waves in Cattle Progesterone Atresia estradiol inhibin FSH Follicular Size Dominance FSH estradiol (-) inhibin (-) Selection FSH estradiol (-) inhibin (-) Recruitment FSH estradiol (-) Ovulation 9 16 21 Day After Ovulation

Follicular Waves in Cattle Progesterone Follicular Size Atresia Dominance Selection Recruitment Ovulation 9 16 21 Day After Ovulation

Follicular Waves in Cattle Progesterone Follicular Size Ovulation 9 16 21 Day After Ovulation

Follicular Waves in Cattle Progesterone Follicular Size Ovulation 9 16 21 Day After Ovulation

Follicular Waves in Cattle Progesterone Dominance Recruitment Selection Ovulation Follicular Size Ovulation 9 16 21 Day After Ovulation

Two Follicular Waves Follicular Size Day After Ovulation Progesterone Dominance Follicular Size Atresia Ovulation Selection Recruitment Ovulation 10 21 Day After Ovulation

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 Theca Internal Granulosa

Theca Interna Granulosa LH Receptor cAMP Cholesterol PKA Testosterone Blood Receptor LH cAMP Cholesterol Testosterone PKA Testosterone Receptor FSH cAMP Estradiol PKA

Theca Interna Selection Granulosa LH Receptor Dominant Follicle cAMP Blood Receptor LH cAMP Receptor LH Selection Dominant Follicle Express LH Receptor cAMP Cholesterol Testosterone PKA Testosterone Receptor FSH cAMP Estradiol PKA

Ovulation

Germinal Epithelium Tunica Albuginea Theca Externa Theca Interna Basement Membrane Granulosa

Blocking of these events in the follicle prevents ovulation. protein synthesis steroid synthesis prostaglandin synthesis plasminogen activator synthesis

Preovulatory LH Surge Ovulation Cumulus Expansion Oocyte Separates From Follicular Wall Ovulation

Cumulus Expansion Hyaluronic Acid and Protein Production Unexpanded

Cumulus and Oocyte Separation

Protein synthesis changes Prostaglandin Synthesis Preovulatory LH Surge Cumulus Expansion Oocyte Separates From Follicular Wall Protein synthesis changes in and around Follicle Plasminogen Activator Progesterone Prostaglandin Synthesis PGE and PGF Ovulation

Preovulatory LH Surge Ovulation Cumulus Increased Blood Expansion Histamine PGE2 Preovulatory LH Surge Increased Blood Flow to Ovary and Follicle Vascular Permeability Plasminogen Cumulus Expansion Oocyte Separates From Follicular Wall Protein synthesis changes in and around Follicle Plasminogen Activator Progesterone Prostaglandin Synthesis PGE and PGF Edema Follicular pressure Ovulation

Preovulatory LH Surge Ovulation Cumulus Increased Blood Expansion Histamine PGE2 Preovulatory LH Surge Increased Blood Flow to Ovary and Follicle Vascular Permeability Plasminogen Cumulus Expansion Oocyte Separates From Follicular Wall Protein synthesis changes in and around Follicle Plasminogen Activator Progesterone Prostaglandin Synthesis PGE and PGF Collagenase (inactive) Follicular Wall Weakens Plasmin Collagenase (active) Edema Follicular pressure Ovulation

Preovulatory LH Surge Ovulation Cumulus Increased Blood Expansion Histamine PGE2 Preovulatory LH Surge Increased Blood Flow to Ovary and Follicle Vascular Permeability Plasminogen Cumulus Expansion Oocyte Separates From Follicular Wall Protein synthesis changes in and around Follicle Plasminogen Activator Progesterone Prostaglandin Synthesis PGE and PGF Collagenase (inactive) Follicular Wall Weakens Plasmin Collagenase (active) Contraction of Smooth Muscle Edema Follicular pressure Ovulation

Types of Ovulators

Spontaneous Ovulators

Induced Ovulators

Nerve endings sensing copulation Induced Ovulators Nerve endings sensing copulation Sensory Neurons Penis Copulation

Hypothalamus Blood LH Time (hr) GnRH Posterior Pit. Stimulation LH Anterior Pit. Spinal Chord

Nerve endings sensing copulation LH Nerve endings sensing copulation Sensory Neurons Penis Copulation

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

Oogenesis Gonadotropin Independent Gonadotropin Dependent Migration to germinal ridge Mitotic divisions Primordial Germ Cells Oogonia Follicle Cells Initiation of Meiosis Interphase DNA synthesis Meiotic prophase begins Prophase of Meiosis leptotene zygotene pachytene diplotene Meiotic Arrest dictyotene Primary Oocyte Growth Gonadotropin Independent zona pellucida formation mRNA production protein synthesis cortical granule formation Gonadotropin Dependent nuclear maturation cytoplasmic maturation

Oogonia in Egg Nest Fetal Pig Ovary

Oogonia and Primary Oocytes

Primary Oocytes in Primordial Follicles

Primary Oocyte in Primary Follicle

Fetal Oocyte Development Mitosis Meiosis Fertilization Birth Cow 280 d Sow 114 d Mouse 19 d

Ovulation of Tertiary Follicle

Formation of the Zona Pellucida Corona Radiata Oocyte Zona Pellucida

Corona Radiata Zona Pellucida Oocyte Gap Junctions

During Oocyte Growth and Before the LH Surge OMI - Oocyte Maturation Inhibitor MPF - Maturation promoting factor GV - germinal vesicle (nucleus) cAMP OMI cAMP PKA GV pre-MPF MPF Gap Junctions Allow Cell to Cell Communication!

The LH Surge Gap Junctions are Destroyed!

Gap Junctions are Destroyed! The LH Surge cAMP Resumption of Meiosis GVBD PKA GV pre-MPF MPF Gap Junctions are Destroyed!

2N 4N (most species) N First polar body Resumption of emitted, arrest at LH Surge Meiosis metaphase II of meiosis 4N 2N N Primary Oocyte Secondary Oocyte Ovulation (most species) Zygote (pronucleate egg) Sperm Penetration

2N 4N Sperm Penetration Ovulation Dog Fox (most species) N First polar body Resumption of emitted, arrest at LH Surge Meiosis metaphase II of meiosis 4N 2N N Ovulation Dog Fox Sperm Penetration Primary Oocyte Secondary Oocyte Ovulation (most species) Zygote (pronucleate egg) Sperm Penetration