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

2. Tonic and Preovulatory Surge of GnRH

3. Hypothalamus GnRH Anterior Pituitary Anterior Pituitary CLFollicle Ovary LH, FSH LH LH, FSH Inhibin (-) Estradiol Progesterone Estradiol (-)

4. Tonic and Preovulatory Surge of GnRH

5. Follicular Phase

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

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

8. Follicular Phase

9. Follicular Progression Primordial Primary Secondary Tertiary

10. Growth and Atresia of Follicles Atresia

11. 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

12. 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 100 Days of Gestation 2.9 million Can increase with superovulation with FSH to stimulate the rescue of follicles which would have undergone atresia Can increase with superovulation with FSH to stimulate the rescue of follicles which would have undergone atresia

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

14. Follicular Waves in Cattle Ovulation Follicular Size Day After Ovulation 91621 FSH Sensitive Pool Recruitment Selection Dominance Atresia

15. Follicular Waves in Cattle Ovulation Follicular Size Day After Ovulation 91621 FSH Sensitive Pool Recruitment Selection Dominance Atresia Progesterone

16. Follicular Waves in Cattle Ovulation Follicular Size Day After Ovulation 91621 Recruitment FSH estradiol (-) Selection FSH estradiol (-) inhibin (-) Dominance FSH estradiol (-) inhibin (-) Atresia estradiol inhibin Progesterone

17. Follicular Waves in Cattle Ovulation Follicular Size Day After Ovulation 91621 Recruitment Selection Dominance Atresia Progesterone

18. Follicular Waves in Cattle Ovulation Follicular Size Day After Ovulation 91621 Progesterone

19. Follicular Waves in Cattle Ovulation Follicular Size Day After Ovulation 91621 Progesterone

20. Follicular Waves in Cattle Ovulation Follicular Size Day After Ovulation 91621 Progesterone Dominance Recruitment Selection Ovulation

21. Two Follicular Waves 10Ovulation21 Follicular Size Recruitment Selection Dominance Atresia Ovulation Day After Ovulation Progesterone

22. Follicular Wave Emergence FSH always controls emergence Increase in FSH precedes emergence

23. 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

24. Gonadotropin Action Within the Follicle

25. Antral Follicle Granulosa Theca Internal

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

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

28. Ovulation

29. Tunica Albuginea Germinal Epithelium Theca Externa Theca Interna Granulosa Basement Membrane

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

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

32. Cumulus Expansion Unexpanded Expanded Hyaluronic Acid and Protein Production

33. Cumulus and Oocyte Separation

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

35. Preovulatory LH Surge Ovulation Increased Blood Flow to Ovary and Follicle Increased Blood Flow to Ovary and Follicle Vascular Permeability Plasminogen Cumulus Expansion Cumulus Expansion Oocyte Separates From Follicular Wall Oocyte Separates From Follicular Wall Protein Synthesis in and around Follicle Protein Synthesis in and around Follicle Plasminogen Activator Plasminogen Activator Progesterone Prostaglandin Synthesis PGE and PGF Prostaglandin Synthesis PGE and PGF

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

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

38. Types of Ovulators

39. Spontaneous Ovulators

40. Induced Ovulators

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

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

43. Sensory Neurons Nerve endings sensing copulation Penis Copulation LH

44. Cats Induced Ovulators Single copulation –Only works 50% of the time Multiple copulations –Higher LH surge

45. 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

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

47. Fetal Oocyte Development Fertilization Birth MitosisMeiosis Mouse 19 d Sow 114 d Cow 280 d

48. Ovulation of Tertiary Follicle

49. Formation of the Zona Pellucida Corona Radiata Zona Pellucida Oocyte

50. Corona Radiata Zona Pellucida Oocyte Gap Junctions

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

52. The LH Surge Gap Junctions are Destroyed!

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

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

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