Animal Science 434 Lecture 10 The Follicular Phase

Animal Science 434 Lecture 10: The Follicular Phase of the Estrous Cycle

Tonic and Preovulatory Surge of Gn. RH

Hypothalamus Progesterone (-) Gn. RH Estradiol (-) Anterior Pituitary Inhibin (-) LH, FSH LH CL Estradiol LH, FSH Ovary Follicle

Tonic and Preovulatory Surge of Gn. RH

Follicular Phase

Hypothalamus Progesterone (-) Gn. RH Estradiol (-) (+) Anterior Pituitary Inhibin (-) LH, FSH LH CL Estradiol LH, FSH Ovary Follicle

Follicular Phase

Follicular Progression Primordial Primary Secondary Tertiary

Growth and Atresia of Follicles Atresia

Fate of follicles and oocytes. Total # of follicles At birth 12 months 100, 000 100 Days of Gestation 75, 000 2. 9 million 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 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 Follicular Size Atresia Recruitment Dominance Ovulation Selection FSH Sensitive Pool Ovulation 9 16 Day After Ovulation 21

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

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

Follicular Waves in Cattle Progesterone Follicular Size Ovulation Dominance FSH, E 2 inhibin, LH Selection FSH, E 2 inhibin, LH Recruitment FSH, E 2 Ovulation 9 16 Day After Ovulation 21

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

Species Variation in Follicular Waves • • • Cattle - 2 or 3 / cycle Cl-progesterone Sheep - 4 or 5 / cycle Pigs - 1 / cycle Cl-progesterone, Horses - 1 / cycle Human - 1 / cycle inhibin

Gonadotropin Action Within the Follicle

Antral Follicle Theca Internal Granulosa

LH Theca Interna Receptor Selection Dominant Follicle Express LH Receptor c. AMP Cholesterol PKA Testosterone LH Receptor c. AMP Testosterone c. AMP PKA Granulosa Estradiol Bloo d FSH

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 Cumulus Expansion Oocyte Separates From Follicular Wall Ovulation

Cumulus Expansion Hyaluronic Acid and Protein Production Unexpanded Expanded

Cumulus and Oocyte Separation

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

Types of Ovulators

Spontaneous Ovulators

Induced Ovulators

Induced Ovulators Nerve endings sensing copulation Copulation Sensory Neurons Penis

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

LH Nerve endings sensing copulation Copulation Sensory Neurons Penis

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 – PGF 2 – Gn. RH – Progestins • Superovulation – FSH – e. CG

Principle of PGF 2 Use • Regress active corpus luteum – Only effective on day 5 - 17 corpus luteum – Not effective on days: ü 1 - 4 (CL not responsive) ü 18 - 21 (CL already regressed)

Induction of Ovulation with PGF 2 Follicular Size Progesterone Ovulation Dominance PGF 2 Selection Recruitment Ovulation 9 16 Day After Ovulation 21

Ovsync Gn. RH PGF 2 Gn. RH Timed AI 7 Days Eliminate current follicular wave 36 - 48 hours Luteolysis 8 - 18 hours 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. This does not regress the CL!!!! Administration: • Injection • Feed • Implant • Pessary or Control Internal Drug Release (CIDR)

Stimulating Follicular Development e. CG or FSH Estrus Ovulation Progesterone From C. L. PGF 2 First Follicular Wave Estrus e. CG or FSH 10 -12 Multiple Ovulations 17

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

Fetal Oocyte Development Mitosis Fertilization Meiosis 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 c. AMP OMI c. AMP GV PKA pre-MPF • MPF - Maturation promoting factor • GV - germinal vesicle (nucleus) Gap Junctions Allow Cell to Cell Communication!

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

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

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