Animal Science 434 The Follicular Phase of the

Animal Science 434 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

Hypothalamus Gn. RH Estradiol (+) Anterior Pituitary Inhibin (-) LH, FSH 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 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 At birth 12 months Total # of follicles 100, 000 100 Days of Gestation 2. 9 million 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 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 Follicular Size Atresia Recruitment Dominance Ovulation Selection FSH Sensitive Pool Ovulation 9 16 Day After Ovulation 21

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 Ovulation FSH Dominance Selection FSH Recruitment 9 FSH estradiol inhibin FSH 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 Follicular Size Progesterone Ovulation 9 16 Day After Ovulation 21

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

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

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

Follicular Wave Emergence • Recruitment = Emergence • FSH always controls emergence • Increase in FSH precedes emergence

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 c. AMP Cholesterol PKA Testosterone FSH Bloo d Receptor c. AMP Testosterone PKA Granulosa Estradiol

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 changes in and around Follicle Progesterone Plasminogen Activator Prostaglandin Synthesis PGE and PGF Oocyte Separates From Follicular Wall Ovulation

Preovulatory LH Surge Cumulus Expansion Protein synthesis changes in and around Follicle Progesterone Plasminogen Activator Histamine PGE 2 Increased Blood Flow to Ovary and Follicle Vascular Prostaglandin Permeability Synthesis PGE and PGF Plasminogen Oocyte Separates From Follicular Wall Edema Ovulation Follicular pressure

Preovulatory LH Surge Cumulus Expansion Protein synthesis changes in and around Follicle Plasminogen Activator Collagenase (inactive) Progesterone Plasmin Histamine PGE 2 Increased Blood Flow to Ovary and Follicle Vascular Prostaglandin Permeability Synthesis PGE and PGF Plasminogen Oocyte Collagenase (active) Separates Follicular Wall From Weakens Follicular Wall Ovulation Edema Follicular pressure

Preovulatory LH Surge Cumulus Expansion Protein synthesis changes in and around Follicle Plasminogen Activator Collagenase (inactive) Progesterone Plasmin Histamine PGE 2 Increased Blood Flow to Ovary and Follicle Vascular Prostaglandin Permeability Synthesis PGE and PGF Plasminogen Oocyte Collagenase (active) Separates Follicular Wall From Weakens Follicular Wall Ovulation Contraction of Smooth Muscle Edema Follicular pressure

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

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

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 Fertilization Meiosis 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 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 Gap Junctions are Destroyed!

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

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

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