Follicle Phase and Ovulation

The Follicle Phase and Ovulation

Overview of Follicle Development

  • Follicle Development Types:

    • Monotocous Species: Ovulate one dominant follicle.

    • Polytocous Species: Ovulate multiple large follicles.

  • Heritability of Ovulation Rate:

    • The ovulation rate is heritable; noted in species such as pigs and sheep (and possibly humans).

Follicles on Ovaries During a Cycle

  • Presence of Follicles in Fertile Animals:

    • Numerous primary (1°), secondary (2°), and tertiary (3°) follicles are always growing in the cortex beneath the surface, with some visible on the surface (>1 mm).

  • Species Differences:

    • Certain species have large follicles only during the late follicle phase, which may include both spontaneous and induced ovulators.

    • Other species (like ruminants) have large/dominant follicles in both the luteal and follicle phases.

Ovulation Enhancement for Embryo Production

  • In various species, ovulation is enhanced to increase the potential for embryo production:

    1. 1 embryo

    2. 2 embryos

    3. 4 embryos

    4. 8 embryos

    5. 16 embryos

    6. 14 embryos

    7. 12 embryos

    8. 10 embryos

    9. 8 embryos

    10. 6 embryos

    11. 4 embryos

    12. 2 embryos

    13. 0 embryos

  • Note: The specific ovulation rates correspond to the number of embryos that can potentially be produced.

Litter-Bearing Species Ovulation Rate

  • Ovulation Rate Impact on Litter Size:

    • The ovulation rate is the first limiting factor to litter size in litter-bearing species.

    • Litter Size vs. Number of Eggs Ovulated:

    • This relationship forms a foundational principle in the reproductive biotechnology of these species.

The Follicle Phase Stages

  • Early Proestrus:

    • No species present dominant or ovulatory follicles.

  • Late Proestrus:

    • All species exhibit one or more dominant or ovulatory follicles.

Key Events Allowing Follicle Phase Start

  • Triggers for the Follicle Phase:

    • Puberty:

    • A signal initiates the advancement of follicles.

    • In Season:

    • Linked to photoperiod responsiveness.

    • Post-Partum Recovery:

    • Luteolysis:

    • Occurs in cycling animals that are not pregnant, often following a period of elevated progesterone.

Sequence of a Follicle Phase: Estrus and Ovulation

  • Key Events and Hormonal Patterns:

    • Concentration of Blood Hormones:

    • Major hormones involved during this sequence include:

      • Progesterone

      • FSH (Follicle-Stimulating Hormone)

      • Inhibin

      • Estradiol

      • GnRH (Gonadotropin-Releasing Hormone)

      • LH (Luteinizing Hormone)

Sequence: Proestrus and Estrus

  • Follicle Growth Dynamics:

    • Selected follicles grow to a large size while others regress (marked as X).

    • Estrogen Feedback:

    • Estrogen (E2) feedback leads to an increase in GnRH pulses and LH pulses.

    • Estrogen Threshold:

    • Reaches a level at which estrus begins (identified as ESTRUS).

    • LH Surge:

    • Leads to ovulation.

    • Days and Blood Concentrations:

    • Estrus occurs around day 9 of the cycle as described by hormone concentrations in the blood.

Follicle Lifespan

  • Recruitment Stages:

    • Primordial Follicles:

    • Leave resting state to enter the growing pool, transitioning from primordial to antral stage (approximately 1 month).

    • Antral Stage:

    • Follicles become sensitive to FSH.

    • Timeframe from antral stage to visibly surface follicles is approximately 1 month.

    • Growth from small to large follicles may take days to weeks.

  • Selection Process:

    • One or more medium follicles grow to the large (ovulatory) size.

    • Enhanced by active estrogen production, leading to increased inhibin production that reduces FSH and competition among follicles.

Follicle Sizes and Receptor Types

  • Follicle Size Classification (Surface Visibility):

    • Small: Follicles with FSH receptors.

    • Medium: Follicles with FSH and LH receptors.

    • Large: Follicles with LH receptors.

Structure of the Follicle

  • Follicular Anatomy Identified:

    1. Germinal Epithelium and Tunica Albuginea

    2. Theca Externa

    3. Theca Interna

    4. Granulosa

    5. Antrum

    6. Basal Lamina

    7. FSH (Follicle-Stimulating Hormone)\n

Steroid Production in Follicles

  • 2-Cell Production Mechanism:

    • The actions of FSH and LH on steroid production are observed in the following manner:

    • Granulosa Cells (C18) respond to FSH, converting androgens into estradiol (E2).

    • Theca Interna Cells (C27, C19) respond to LH to produce androgens.

    • Theca Externa: Contains capillaries; LH binds to receptors in theca cells to assist steroid production.

    • Paracrine Effects: The interaction between theca and granulosa cells leads to enhanced steroid production.

Comparative Follicle Size in Various Species

  • Sizes of Ovulatory Follicles (in mm):

    • Rat: 0.7 mm

    • Queen: 2 mm

    • Bitch: 7 mm

    • Ewe: 10 mm

    • Sow: 12 mm

    • Woman: 18 mm

    • Cow: 18 mm

    • Mare: 50 mm

Follicle Growth in Pigs

  • Surface Follicle Growth:

    • Over 4-5 days, pigs select ovulatory follicles with the following counts:

    • Small: 40

    • Medium: 25

    • Large: 18

Follicle Phase in Horses

  • Mare Follicle Phase:

    • Over 6 days, a mare develops and selects a single dominant large follicle which is retained until ovulation.

    • Estrus phase maintained for 5-7 days.

Follicle Development Waves in Cattle

  • Wave Patterns During the Estrous Cycle:

    • Cattle exhibit three waves of follicular development across weeks 1, 2, and 3.

    • Graphical Representation:

    • Shows fluctuation of dominant (DF), medium (MF), and small follicles (SF) across the estrus cycle duration (18-22 days).

Female Follicle Dynamics in Primates

  • Human Follicle Development Timeline:

    • Day 15: Recruitment of 3-30 follicles for growth post-ovulation.

    • Day 5: Selection of a cohort for advancement.

    • Day 9: Dominance and final selection process.

    • Day 14: Ovulation occurs.

Reproductive Features in Rats

  • Unique Rat Reproductive Dynamics:

    • Ovulated follicles have minimal luteal cells and produce limited progesterone.

    • Absence of cervical stimulation at estrus leads to no increase in PRL (prolactin) resulting in no development of CL (corpus luteum).

    • Cervical stimulation at estrus can induce pseudopregnancy lasting 12 days.

Canine Reproductive Cycle

  • Dog's Proestrus Phase:

    • Duration: 9 days, occurring 1-3 times per year.

    • Dogs will ovulate and form a corpus luteum (CL) lasting 60 days.

    • Citation: Payan-Carreira, R., Miranda, S., & Nizanski, W. (2011). Artificial Insemination in Dogs.

Feline Reproductive Behaviors

  • Cat's Reproductive Cycle:

    • During the season, cats may experience repeated proestrus periods lasting 10 days.

    • Peak estradiol occurs over 3 days.

    • Cats ovulate and form a CL only if mated; the CL lasts 60 days, regardless of pregnancy status.

Ovulation Types and Mechanisms

  • Spontaneous Ovulation:

    • Characterized by pre-ovulatory LH surge.

    • Estrogen induces dilation of ovarian arteries leading to increased blood flow and capillary permeability in the antrum.

    • After the LH surge, theca cells convert androgens into progesterone, stimulating collagenase production.

    • Resulting in the breakdown of tunica albuginea and rupture, leading to ovulation (egg and fluid expulsion).

  • Induced Ovulators:

    • During breeding seasons (spring/fall), large follicles develop and produce estrogen.

    • Vaginal or cervical stimulation by males causes neural action potentials through afferent nerve pathways to the CNS.

    • Resulting signals in the hypothalamus induce GnRH and LH surges, which leads to ovulation.

    • Ovulation can also be inhibited through hormonal means.

Comparative Estrous Cycles Overview

  • Key Cycle and Estrus Lengths for Various Species:

    • Pig:

      • Follicle Phase: 6 days

      • Estrus Duration: 2 days

      • Overall Cycle Length: 21 days

    • Cow:

      • Follicle Phase: 3-4 days

      • Estrus Duration: <1 day

      • Overall Cycle Length: 21 days

    • Horse:

      • Follicle Phase: 6 days

      • Estrus Duration: 5-7 days

      • Overall Cycle Length: 21 days

    • Sheep:

      • Follicle Phase: 3-4 days

      • Estrus Duration: <1 day

      • Overall Cycle Length: 17 days

    • Cat:

      • Follicle Phase: 9 days

      • Estrus Duration: 7 days

      • Overall Cycle Length: 9 days (repeats)

    • Dog:

      • Follicle Phase: 9 days

      • Estrus Duration: 9 days

    • Woman:

      • Follicle Phase: 14 days

      • Overall Cycle Length: 28 days

    • Rodent:

      • Follicle Phase: 3 days

      • Estrus Duration: <1 day

      • Overall Cycle Length: 5 days