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Ovarian Changes During the Menstrual Cycle

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Overview

• Ovarian cycle - follicular phase + luteal phase
• Endometrial cycle - menstrual + proliferative + secretory phases

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Diagram 1 - Ovarian & Endometrial Cycle Timeline

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Diagram 2 - Anatomy of the Ovary (Follicle Stages)

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Diagram 3 - Hormonal Changes During the Menstrual Cycle

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Diagram 4 - HPO Axis Feedback During Each Phase

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Phase 1: Follicular Phase (Days 0-14)

1A. Folliculogenesis

• FSH acts on granulosa cells (only ovarian cells with FSH receptors): stimulates growth and estradiol synthesis
• LH acts on theca cells: stimulates androgen (androstenedione) production
• Androstenedione diffuses to granulosa cells where aromatase converts it to estradiol (Two-cell, two-gonadotropin theory)

1B. Dominant Follicle Selection (Days 5-7)

• Has the most FSH receptors (FSH-independent survival)
• Has highest aromatase activity → highest estradiol/androgen ratio
• Receives greater blood supply to its theca

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Flowchart 1 - Follicular Phase Events

Day 0-4: Menses. FSH rises (due to loss of corpus luteum progesterone)
         ↓
Day 1-5: Cohort of primordial follicles recruited
         ↓ FSH + LH
Day 5-7: One DOMINANT follicle selected
         ↓ FSH stimulates granulosa cells
         ↓ LH stimulates theca cells → androstenedione → aromatase → ESTRADIOL ↑
Day 7-12: Estradiol RISES → negative feedback on hypothalamus/pituitary
          → FSH and LH levels slightly fall
          → Non-dominant follicles undergo ATRESIA
Day 12-13: Estradiol surges above threshold (~200 pg/mL for ≥2 days)
           → Feedback SWITCHES from NEGATIVE → POSITIVE

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Phase 2: Ovulation (Day 14)

• Peak estradiol from the dominant follicle acts on the hypothalamus (positive feedback)
• GnRH pulse frequency and amplitude increase
• Anterior pituitary releases a massive LH surge (~3x baseline), peaking ~12 hours after onset
• LH surge lasts ~48 hours; ovulation occurs ~36 hours after surge onset

1. Primary oocyte (arrested in prophase I since fetal life) resumes meiosis I → extrudes first polar body → becomes secondary oocyte (arrested in metaphase II)
2. Cumulus oophorus expands (hyaluronidase synthesis stimulated by FSH)
3. Oocyte-cumulus complex breaks free and floats in antrum
4. Follicle wall thins and ruptures under prostaglandin and protease action
5. Oocyte + corona radiata discharged into peritoneal cavity → swept into fallopian tube

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Flowchart 2 - Ovulatory Mechanism

Estradiol > 200 pg/mL for ≥ 2 days
        ↓ (Positive feedback)
Hypothalamus: GnRH pulse frequency ↑↑
        ↓
Anterior pituitary: LH SURGE (peak ~80 mU/mL) + FSH surge
        ↓ (~36 hours later)
Dominant Graafian follicle RUPTURES
        ↓
Oocyte released → Ovulation
        ↓
Secondary oocyte + corona radiata → fallopian tube

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Phase 3: Luteal Phase (Days 14-28)

3A. Formation of the Corpus Luteum

• Granulosa-lutein cells: Large, pale cells; produce progesterone and estradiol
• Theca-lutein cells: Smaller; produce androgens (precursors for estradiol)
• The corpus luteum is highly vascularized (angiogenesis stimulated by VEGF)
• Begins producing progesterone and estradiol within 1-2 days of ovulation

3B. Hormonal Function

3C. Fate of the Corpus Luteum

• Corpus luteum begins degenerating at days 20-22 (luteolysis)
• Mechanism not fully understood; local prostaglandins and falling LH play roles
• Progesterone and estradiol fall sharply by day 26-28
• Withdrawal of hormonal support → endometrial shedding (menses)
• Corpus luteum becomes the corpus albicans (white scar tissue)
• FSH rises again → new follicular cohort recruited → new cycle begins

• Blastocyst implants ~6-7 days after ovulation
• Trophoblast secretes human chorionic gonadotropin (hCG)
• hCG mimics LH → rescues and maintains the corpus luteum
• Corpus luteum continues producing progesterone and estradiol until the placenta takes over (~8-10 weeks)
• No menses occurs (pregnancy maintained)

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Flowchart 3 - Luteal Phase and Its Outcome

Ovulation (Day 14)
        ↓
Corpus luteum forms (luteinization by LH)
        ↓
Progesterone ↑↑ + Estradiol ↑ (peaks day 20-22)
        ↓ negative feedback
FSH and LH remain LOW
        ↓
         ┌──────────────────────┬───────────────────────────┐
         │ NO fertilization     │ Fertilization occurs       │
         ↓                      ↓                            │
Corpus luteum degenerates   Blastocyst → hCG secreted       │
(days 20-22)                        ↓                        │
Progesterone/Estradiol ↓↓   Corpus luteum RESCUED           │
        ↓                   Progesterone maintained         │
Endometrial shedding        No menses → Pregnancy           │
(Menses, days 0-4)                                          │
FSH rises → New follicle cohort recruited

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Summary Table: Ovarian Changes at a Glance

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Key Points for Exam (15-mark Answer)

1. Ovarian cycle = follicular phase (days 0-14) + luteal phase (days 14-28); the luteal phase is constant at 14 days; variability in cycle length is due to the follicular phase.
2. Folliculogenesis proceeds: primordial → primary → secondary → tertiary (antral) → Graafian follicle; most undergo atresia; only one dominant follicle survives each cycle.
3. Two-cell, two-gonadotropin theory: LH acts on theca cells (androgen) → FSH acts on granulosa cells (aromatase → estradiol).
4. Positive feedback - when estradiol exceeds ~200 pg/mL for ≥2 days, it switches from negative to positive feedback, triggering the LH surge and ovulation.
5. LH surge - peaks ~12 hours after onset; ovulation ~36 hours later; initiates completion of meiosis I by the oocyte.
6. Corpus luteum - formed from luteinized granulosa and theca cells; produces progesterone (dominant) and estradiol; maintained by hCG in pregnancy, degenerates in ~14 days if no pregnancy.
7. Corpus albicans - white avascular scar replacing the degenerated corpus luteum.
8. Inhibin A (from corpus luteum) and Inhibin B (from granulosa cells) selectively suppress FSH without affecting LH.

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