Lecture 10: The Follicular Phase of the Estrous Cycle Animal Science 434 Lecture 10: 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 (-) 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 grow to tertiary characteristic and degenerate. 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 Can increase with superovulation with FSH to stimulate the rescue of follicles which would have undergone atresia

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

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 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 Dominance Recruitment Selection Ovulation Follicular Size FSH, E2 inhibin, LH FSH, E2 inhibin, LH FSH, E2 Ovulation 9 16 21 Day After Ovulation

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

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 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

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

Types of Ovulators

Spontaneous Ovulators

Induced Ovulators

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

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

Manipulating Ovulation Hormonal induction of ovulation PGF2a GnRH Progestins Superovulation FSH eCG

Principle of PGF2a Use Regress active corpus luteum Only effective on day 5 - 17 corpus luteum Not effective on days: 1 - 4 (CL not responsive) 18 - 21 (CL already regressed)

Induction of Ovulation with PGF2a Progesterone Dominance Recruitment Selection Ovulation Follicular Size PGF2 Ovulation 9 16 21 Day After Ovulation

Eliminate current follicular wave Ovsync GnRH PGF2 GnRH 8 - 18 hours Timed AI 7 Days 36 - 48 hours Eliminate current follicular wave Luteolysis Ovulates dominant follicle

Use of Progestogens Principle: Maintain the cow under the influence of progesterone until corpus luteum regresses, remove progesterone - animal respond to progesterone with estrus and ovulation 2-5 days later. Administration: Injection Feed Implant Pessary or Control Internal Drug Release (CIDR) This does not regress the CL!!!!

Stimulating Follicular Development eCG or FSH Multiple Ovulations Ovulation Estrus Estrus Progesterone From C.L. Estrus eCG or FSH First Follicular Wave 10-12 PGF2a 17

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

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

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!

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

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

Hormonal Production by Follicles Recruitment Estradiol Selection Estradiol, Inhibin Dominant Estradiol, Inhibin Atretic Androgen or No steroid