Hub 1 — Core Concepts

Female Reproductive System Active Drills

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Lecture 03 · Repro Block · Female Reproductive Histology & Menstrual Cycle
Primary: RPD03 Lecture Guide (HoyaDocs)
Lecturer: Histology
Review: Junqueira's Basic Histology Ch. 22
Topics: Follicles · Oviduct · Uterus · Menstrual Cycle · External Genitalia · Mammary
Hub Progression: Hub 1 — Core Concepts → →
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Flashcards
10
Fill-in-Blank
3
Ordering Drills
3
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8
Test Traps
Click a card to flip · 16 cards totalFemale Repro Histology
Ovary Organization
Name the three basic regions of the adult ovary from outermost to innermost, and what each contains.
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Answer
1. Germinal epithelium — simple cuboidal surface; underlying tunica albuginea (dense CT).

2. Cortex — connective tissue containing ovarian follicles in varying stages.

3. Medulla — loose CT with blood vessels, nerves, lymphatics.

Clinical: Most ovarian cancers arise from the germinal epithelium.
Primordial Follicle
What cells surround the oocyte in a primordial follicle, and at what stage of meiosis is the oocyte arrested?
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Answer
Primordial follicle: oocyte surrounded by a single layer of squamous follicular cells (+ stromal cells outside).

All follicles exist in this stage at birth, arrested in prophase I of meiosis.

Do NOT respond to FSH until puberty. Each cycle, ~20 are recruited and upgrade their follicular cells to columnar/granular (granulosa cells).
Primary Follicles
Differentiate unilaminar vs. multilaminar primary follicles. When does the zona pellucida form?
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Answer
Unilaminar primary follicle: oocyte surrounded by a single layer of granulosa cells (cuboidal/columnar) + basal lamina. Zona pellucida begins forming.

Multilaminar primary follicle: hyperplasia → multiple layers of granulosa cells. Now the zona pellucida is fully visible (proteoglycan-rich ECM between oocyte & granulosa — synthesized by BOTH). Stromal cells begin differentiating into theca interna.
Secondary (Antral) Follicle
What defines the secondary follicle? What is OMI, and what does the theca interna do that the theca externa doesn't?
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Answer
Defined by the antrum — a fluid-filled space containing hyaluronic acid-rich liquor folliculi with OMI (Oocyte Meiosis Inhibitor), which arrests the oocyte in prophase II.

Theca interna: steroidogenic cells → produce androstenedione → aromatized by granulosa cells into estrogen (2-cell hypothesis).

Theca externa: mainly connective tissue — structural only.
Graafian (Tertiary) Follicle
What are the corona radiata and cumulus oophorus, and where is the oocyte located in a Graafian follicle?
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Answer
Graafian follicle = dominant follicle. Oocyte is eccentrically located, surrounded by granulosa cells connected to the mature follicle by a granulosa pedicle.

Corona radiata: innermost single layer of granulosa cells directly hugging the oocyte (travels WITH the oocyte at ovulation).

Cumulus oophorus: accumulations of granulosa cells continuous with the pedicle — attaches the oocyte complex to the follicle wall.
Ovulation — LH Surge
What triggers the LH surge, and what happens to meiosis at ovulation?
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Answer
Rising estrogen (from the dominant Graafian follicle) → LH surge.

Follicle ruptures → oocyte releases with corona radiata attached = ovulation.

LH overrides OMI → meiosis resumes, proceeds through meiosis I, then arrests again in metaphase II — where it stays until fertilization.
Corpus Luteum
After ovulation, what do granulosa and theca interna cells become, and what do they each now secrete?
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Answer
Remnants of the ruptured Graafian follicle → corpus luteum ("yellow body"), a temporary endocrine gland.

Granulosa cells (estrogen-producing) → granulosa lutein cells → now produce progesterone.

Theca interna cells (androstenedione-secreting) → theca lutein cells → now produce estrogen.

If no pregnancy: CL regresses → corpus albicans (white scar).
Oviduct — 4 Parts
Name the four parts of the fallopian tube from ovary to uterus and their key functions.
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Answer
1. Infundibulum — initial trumpet-shaped segment; fimbriae move to trap the ovum.

2. Ampulla — most dilated, complex mucosal folding; site of fertilization.

3. Isthmus — shortest; connects to uterus.

4. Intramural (pars interstitialis) — passes through uterine wall.

Mnemonic: IAII = "I Ain't Implanting Inside."
Oviduct Epithelium
What two cell types line the fallopian tube, and what hormone maintains their function?
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Answer
Simple columnar epithelium with two cell types — both estrogen-dependent:

Ciliated cells: help move the ovum/zygote through the tube.

Non-ciliated peg (secretory) cells: secrete proteins to nurture the zygote.

Wall layers: mucosa → muscularis (inner circular + outer longitudinal) → serosa.
Uterus — 3 Wall Layers
Name the three layers of the uterine wall and the two sublayers of the endometrium. Which sublayer sheds during menses?
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Answer
1. Endometrium — innermost; simple columnar (ciliated + secretory) + simple tubular glands.
• Functionalis: superficial layer sheds at menstruation (supplied by spiral/coiled arteries).
• Basalis: deep layer, provides cells to regenerate the functionalis (supplied by straight arteries).

2. Myometrium — thickest middle smooth muscle; hypertrophy & hyperplasia during pregnancy.

3. Perimetrium — outer CT; forms part of broad ligament.
HPO Axis
Trace the hypothalamic-pituitary-ovarian axis: hormones, targets, and feedback loops.
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Answer
Hypothalamus: GnRH → ant. pituitary
Ant. pituitary:
• FSH → stimulates follicular phase
• LH → stimulates ovulation + corpus luteum

Follicles → estrogen → negative feedback on hypothalamus (GnRH) UNTIL a threshold → positive feedback → LH surge.

Corpus luteum → estrogen + progesterone → negative feedback on hypothalamus + pituitary.
Menstrual Cycle Phases
Name and time the four phases of the menstrual cycle and the dominant hormone of each.
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Answer
1. Menses (day 0–5): ↓estrogen, ↓progesterone (CL has degenerated).
2. Proliferative (day 6–14) / Follicular: estrogen rises → endometrium thickens (2–3×), straight tubular glands elongate.
3. Secretory (day 15–28) / Luteal: CL produces estrogen + progesterone → endometrium thickens more, glands become coiled & convoluted, spiral arteries elongate; glands secrete for implantation.
4. Ischemic (late day 28): CL degenerates → ↓E, ↓P → vasospasm of spiral arteries → ischemic necrosis of functionalis → menses restart.
Cervix — Epithelium & T-Zone
What type of epithelium lines the ectocervix vs. endocervix, and where does cervical cancer most often arise?
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Answer
Ectocervix (projects into vagina): stratified squamous non-keratinized.

Endocervix (canal): simple columnar glandular (secretes mucus).

Transformation zone (T-zone): the junction between squamous and columnar — where HPV (16, 18) → most cervical cancers arise. Gardasil prevents.
Vagina — Histology
What are the three layers of the vaginal wall and the type of epithelium in the mucosa?
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Answer
1. Mucosa: stratified squamous non-keratinized epithelium (like ectocervix); no glands (lubricated by cervical mucus + Bartholin glands).

2. Muscularis: smooth muscle — inner circular, outer longitudinal.

3. Serosa/Adventitia: dense CT + elastic fibers.

Key: estrogen stimulates glycogen deposition → fermented by Lactobacillus → acidic pH.
External Genitalia & Glands
Describe the histology of the clitoris, labia minora, and labia majora. Name the homologues of Bartholin's and Skene glands.
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Answer
Clitoris: homologue of the penis — venous erectile tissue (corpora cavernosa), blood vessels, sensory nerves (Pacinian corpuscles).
Labia minora: core spongy tissue + keratinized stratified squamous epithelium.
Labia majora: skin + adipose + thin smooth muscle; hair, sebaceous, sweat glands; keratinized stratified squamous.

Bartholin's glands (greater vestibular) — simple columnar; mucous lubricant → homologue: bulbourethral (Cowper) glands.
Skene glands (paraurethral) — pseudostratified/simple columnar; lubricant → homologue: prostate.
Mammary Glands
What is the basic structural unit of the mammary gland? What changes in active (lactating) vs. inactive glands?
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Answer
Compound tubuloalveolar glands grouped into lobes separated by dense CT (and fat). Milk drains through branching ducts → lactiferous ducts → lactiferous sinuses → nipple.

Inactive gland: predominantly ducts + adipose/CT, few secretory units.
Active (lactating) gland: extensive tubuloalveolar secretory units with lumens full of milk; reduced stromal fat.

Changes driven by: estrogen (ducts), progesterone (alveoli), prolactin (milk production), oxytocin (let-down reflex).
FIB 01 — Ovary Zones
The three basic regions of an adult ovary are: the outer ___________ epithelium (simple cuboidal), the ___________ (contains follicles), and the innermost ___________ (loose CT with vessels).
Hint: Most ovarian cancers arise from the outermost layer.
FIB 02 — Meiotic Arrest
All primordial follicles at birth are arrested in ___________ I of meiosis. The antral follicle's OMI (Oocyte Meiosis Inhibitor) keeps them arrested in ___________ II. After the LH surge at ovulation, meiosis resumes but arrests again in ___________ II, where it stays until fertilization.
Hint: Prophase I → Prophase II → Metaphase II.
FIB 03 — Two-Cell Model
In the two-cell hypothesis, ___________ interna cells produce androstenedione (in response to LH), which is then aromatized into estrogen by the ___________ cells (in response to FSH).
Hint: "LH likes the theca; FSH feeds the granulosa."
FIB 04 — Corpus Luteum
After ovulation, granulosa cells become granulosa lutein cells and now produce ___________, while theca interna cells become theca lutein cells and now produce ___________. If pregnancy doesn't occur, the CL regresses into a white scar called the corpus ___________.
FIB 05 — Oviduct Parts
The 4 parts of the fallopian tube from ovary to uterus are: ___________ (with fimbriae), ___________ (site of fertilization), ___________ (shortest), and intramural portion.
FIB 06 — Endometrium Layers
The endometrium has two sublayers: the superficial ___________ is shed during menstruation, and the deep ___________ regenerates the lining. The functionalis is supplied by ___________ (coiled) arteries.
Hint: Spiral arteries are hormonally responsive; straight arteries supply the deep layer.
FIB 07 — Menstrual Cycle Phases
Days 0–5 = ___________ phase. Days 6–14 = ___________ (or follicular) phase, driven by estrogen. Days 15–28 = ___________ (or luteal) phase, driven by progesterone.
FIB 08 — LH Surge & Ovulation
Rising ___________ (hormone) from the dominant Graafian follicle triggers the ___________ surge, which overrides OMI and causes the follicle to rupture at ovulation (~day ___________ of a 28-day cycle).
Hint: Estrogen switches from negative to positive feedback when it reaches a threshold.
FIB 09 — Cervix Epithelium
The ectocervix is lined by stratified squamous ___________-keratinized epithelium; the endocervix is lined by simple ___________ epithelium. The junction between the two (the ___________ zone) is where cervical cancer most frequently arises.
Hint: HPV 16/18 cause most cervical cancers here — Pap smears sample this zone.
FIB 10 — Vestibular Gland Homologues
Bartholin's (greater vestibular) glands secrete mucus for lubrication and are homologous to the male ___________ glands. Skene (paraurethral) glands secrete lubricating fluid and are homologous to the male ___________.
Hint: "Big Bar = Bulbourethral; Skene = Prostate."
Instructions: Drag and drop the items into the correct order, then click "Check Order." Use "Show Answer" if you get stuck.
Drill 1 — Follicular Stages: Primordial → Corpus Albicans
Arrange these 7 stages of follicle maturation from earliest (at birth) to final degeneration.
⠿Corpus luteum — granulosa + theca lutein cells produce progesterone + estrogen
⠿Unilaminar primary follicle — single layer of granulosa cells; zona pellucida begins forming
⠿Ovulation — LH surge ruptures follicle; oocyte + corona radiata released
⠿Primordial follicle — oocyte + single squamous follicular cell layer (arrested in prophase I at birth)
⠿Multilaminar primary follicle — several granulosa layers + theca interna differentiates
⠿Corpus albicans — white scar in cortex after CL regresses (no pregnancy)
⠿Secondary/Graafian follicle — antrum with OMI; dominant; corona radiata + cumulus oophorus
  1. Primordial follicle — present at birth; arrested prophase I
  2. Unilaminar primary — single layer granulosa; zona pellucida starts
  3. Multilaminar primary — several granulosa layers; theca interna forms
  4. Secondary → Graafian — antrum; corona radiata; cumulus oophorus
  5. Ovulation — LH surge; oocyte + corona radiata released
  6. Corpus luteum — granulosa lutein (P) + theca lutein (E)
  7. Corpus albicans — regression to scar (if no pregnancy)
Drill 2 — 28-Day Menstrual Cycle: Correct Sequence
Arrange the 6 events of the menstrual cycle in chronological order (starting at day 0).
⠿Secretory (luteal) phase — CL makes E + P; glands coil; spiral arteries elongate (days 15–27)
⠿Proliferative (follicular) phase — rising estrogen thickens endometrium 2–3× (days 6–13)
⠿Menses (days 0–5) — low E & P from degenerating CL → functionalis sloughs
⠿LH surge — triggered by estrogen threshold (positive feedback)
⠿Ischemic phase — CL degenerates → ↓E/P → spiral artery vasoconstriction → necrosis → menses restart
⠿Ovulation (day 14) — follicle ruptures; oocyte released
  1. Menses (days 0–5) — ↓E, ↓P, shedding functionalis
  2. Proliferative phase (days 6–13) — estrogen thickens endometrium
  3. LH surge — estrogen positive feedback triggers it
  4. Ovulation (day 14)
  5. Secretory phase (days 15–27) — CL makes E + P; glands coil
  6. Ischemic phase — CL degenerates → menstruation begins next cycle
Drill 3 — HPO Signaling Cascade at Ovulation
Arrange these 6 steps in the correct order of endocrine signaling at mid-cycle.
⠿LH surge — overrides OMI, resumes meiosis; triggers follicular rupture
⠿Ant. pituitary releases FSH → stimulates growing follicles; promotes granulosa aromatase
⠿Oocyte arrests in metaphase II; corona radiata travels with it down the oviduct
⠿Hypothalamus releases GnRH pulses
⠿Estrogen passes threshold → SWITCHES to positive feedback on hypothalamus/pituitary
⠿Follicles produce rising estrogen (2-cell: theca → androgen → granulosa aromatizes → estrogen)
  1. GnRH pulses from hypothalamus
  2. FSH release — stimulates granulosa aromatase
  3. Rising estrogen from 2-cell theca–granulosa unit
  4. Positive feedback switch — estrogen now stimulates LH release
  5. LH surge — resumes meiosis; ruptures follicle
  6. Oocyte released, arrests in metaphase II, awaits fertilization
Instructions: Click an item on the left, then click its match on the right. Correct pairs turn green; wrong pairs flash red.
Set 1 — Follicle Stage → Defining Feature
Match each follicle stage to its most distinguishing histologic feature.
Follicle Stage
Primordial follicle
Multilaminar primary follicle
Secondary (antral) follicle
Graafian (tertiary) follicle
Corpus luteum
Defining Feature
Cumulus oophorus + corona radiata; eccentric oocyte
Single layer of squamous follicular cells; arrested prophase I
Granulosa lutein (P) + theca lutein (E) cells — post-ovulation endocrine gland
Antrum with OMI (arrests prophase II); theca interna starts aromatization
Multiple granulosa layers + zona pellucida + forming theca interna
Score: 0/5 correct
Set 2 — Female Reproductive Structure → Epithelium
Match each anatomic region to the epithelium that lines it.
Structure
Fallopian tube mucosa
Endocervical canal
Ectocervix / vagina
Labia minora (surface)
Urethra (female)
Epithelium
Stratified squamous NON-keratinized
Simple columnar — ciliated + secretory (peg) cells
Pseudostratified columnar
Stratified squamous KERATINIZED
Simple columnar (glandular, mucus-secreting)
Score: 0/5 correct
Set 3 — Ovarian Cell/Structure → Hormone Produced
Match each cell type or endocrine structure to the hormone it makes.
Cell / Structure
Theca interna cells
Granulosa cells (pre-ovulation)
Granulosa lutein cells
Theca lutein cells
Placenta (after week 10)
Primary Hormone
Progesterone (main post-ovulation product)
Androstenedione (LH-stimulated precursor)
Estrogen + progesterone (corpus luteum-placental shift)
Estrogen (aromatizes theca's androgens)
Estrogen (in the corpus luteum)
Score: 0/5 correct
Test Trap Mode: Each statement is either TRUE or FALSE as written. Many are designed to catch common exam errors. Click T or F — then read the explanation carefully.
Trap 01 — Oocyte Arrest
"At birth, all primordial follicles contain oocytes arrested in metaphase II of meiosis."
FALSE. Primordial follicles are arrested in prophase I at birth — where they stay until puberty. After the LH surge at ovulation, meiosis resumes and re-arrests in metaphase II. Metaphase II arrest only occurs AFTER ovulation and is only broken by fertilization. Classic order: prophase I → prophase II (in antral follicles, via OMI) → metaphase II.
Trap 02 — 2-Cell Hypothesis
"Granulosa cells produce androgens, which theca interna cells then convert into estrogen."
FALSE. Completely reversed. The theca interna cells (LH-stimulated) produce androstenedione, which the granulosa cells (FSH-stimulated, expressing aromatase) convert into estrogen. Mnemonic: "LH likes L-theca; FSH feeds F-granulosa." This is the classic 2-cell 2-gonadotropin model.
Trap 03 — Corpus Luteum
"In the corpus luteum, granulosa lutein cells still produce estrogen while theca lutein cells now produce progesterone."
FALSE. Also reversed. In the CL, granulosa lutein cells NOW make progesterone (their main CL product) — a switch from the estrogen they made before ovulation. Theca lutein cells now make estrogen — also a switch from androstenedione. This hormone "swap" is why the corpus luteum secretes both progesterone (dominant) + estrogen in the secretory phase.
Trap 04 — Endometrial Regeneration
"After menstruation, the functionalis regenerates the basalis."
FALSE. Backwards. The basalis (deep layer) is preserved during menses and regenerates the functionalis (superficial layer) in the proliferative phase. The functionalis is what sheds. Basalis is supplied by straight arteries (not hormonally sensitive), while functionalis is supplied by spiral/coiled arteries (estrogen/progesterone-responsive; constrict during ischemic phase).
Trap 05 — Ectocervix Epithelium
"The ectocervix is lined by stratified squamous KERATINIZED epithelium, like the skin."
FALSE. The ectocervix (and vagina) are lined by stratified squamous NON-keratinized epithelium — because they are moist internal surfaces. Keratinization is reserved for dry external surfaces (skin, labia minora/majora surface). The non-keratinized ectocervix meets the simple columnar endocervix at the transformation zone, the primary site of HPV-driven cervical cancer.
Trap 06 — Fertilization Site
"Fertilization most commonly occurs in the isthmus of the fallopian tube because it is the shortest segment."
FALSE. Fertilization occurs in the ampulla, not the isthmus. The ampulla is the longest and most dilated segment with complex mucosal folds that create a favorable environment (transudative fluid accumulation). Sperm travel uterus → isthmus → ampulla, where they encounter the ovum. The isthmus is the shortest segment closer to the uterus. Ectopic pregnancy most commonly occurs in the ampulla for the same reason.
Trap 07 — Menstrual Cycle Timing
"The luteal (secretory) phase varies considerably in length, while the follicular (proliferative) phase is fixed at ~14 days."
FALSE. Reversed. The luteal phase is FIXED at ~14 days (determined by corpus luteum lifespan — CL degenerates after ~14 days if no hCG). The follicular phase is VARIABLE — this is why cycle length differs between women. Clinical pearl: ovulation is ~14 days BEFORE the next menstrual period (not 14 days after the current one).
Trap 08 — Corpus Luteum-Placental Shift
"If pregnancy occurs, the corpus luteum must produce progesterone for the entire 9-month gestation."
FALSE. The corpus luteum-placental shift: hCG from the implanting blastocyst maintains the CL through the first trimester. Around weeks 8–10, the placenta takes over production of progesterone and estrogen — and the CL gradually regresses. Clinical relevance: removing the CL (e.g., oophorectomy) before week 10 risks miscarriage; after that, the placenta alone sustains pregnancy.
Follicular Stages — Full Reference
StageGranulosa LayerOocyte StageDefining Features
PrimordialSingle squamous layerProphase I (arrested)Present at birth; does not respond to FSH until puberty
Unilaminar primarySingle cuboidal/columnar layerProphase IZona pellucida begins forming; basal lamina present
Multilaminar primaryMultiple granulosa layersProphase IZona pellucida fully developed; theca interna starts
Secondary (Antral)Multilayered + antrumProphase II (OMI-arrested)Antrum with liquor folliculi + OMI; theca interna → androstenedione
Graafian (Tertiary)Corona radiata + cumulus oophorusProphase IIDominant follicle; eccentric oocyte attached by pedicle
OvulationReleased (corona radiata)Metaphase II (post-LH surge)LH surge overrides OMI; follicle ruptures
Corpus luteumGranulosa lutein → progesterone—Theca lutein → estrogen; temporary endocrine gland
Corpus albicansFibrous scar—CL degeneration if no pregnancy; white connective tissue
Female Reproductive Tract — Epithelium Summary
StructureEpitheliumStep 1 Hook
Ovary (surface)Simple cuboidal (germinal epithelium)Source of most ovarian cancers (epithelial)
Fallopian tubeSimple columnar: ciliated + peg (secretory)Estrogen-dependent; salpingitis → PID → tubal infertility/ectopic
Uterus — endometriumSimple columnar (ciliated + secretory) + simple tubular glandsFunctionalis sheds w/ menses; basalis regenerates
EndocervixSimple columnar (glandular)Mucus-secreting; hostile in luteal phase
EctocervixStratified squamous NON-keratinizedHPV 16/18 infects T-zone → cervical cancer
VaginaStratified squamous NON-keratinizedEstrogen → glycogen → Lactobacillus → ↓pH
Labia minora surfaceStratified squamous KERATINIZEDExternal skin-like
Labia majora surfaceStratified squamous KERATINIZED (+ hair/sebaceous)True skin with adnexae
Urethra (♀)Pseudostratified columnarShort (~4 cm) → ↑UTI risk
Bartholin's glandsSimple columnar (mucus)Bartholin cyst/abscess; homolog of Cowper
Skene glandsPseudostratified/simple columnarHomolog of prostate
Menstrual Cycle — Hormonal & Endometrial Events
PhaseDaysOvaryEndometriumDominant Hormone
Menses0–5Follicles begin maturingFunctionalis sloughing↓ E, ↓ P
Proliferative (Follicular)6–13Dominant follicle maturesFunctionalis regenerates from basalis; straight tubular glands formEstrogen (rising)
Ovulation14Graafian follicle rupturesTransitions to secretoryLH surge
Secretory (Luteal)15–27Corpus luteumGlands become coiled/tortuous; spiral arteries elongate; glandular secretions peakProgesterone (dominant) + estrogen
Ischemic28CL degenerates (corpus albicans)Spiral artery vasoconstriction → necrosis of functionalis↓ E, ↓ P (sharp drop)
Female ↔ Male Homologues & Clinical Hooks
Female StructureMale HomologClinical Hook
OvaryTestisGonadal ridge → gonad
ClitorisGlans/shaft of penisGenital tubercle; erectile tissue + sensory nerves
Labia minoraPenile urethra (fused)Urethral folds — unfused in ♀
Labia majoraScrotumLabioscrotal swellings — unfused in ♀
Bartholin glandsBulbourethral (Cowper) glandsCyst/abscess at 5 & 7 o'clock of vaginal introitus
Skene glandsProstate glandParaurethral; occasionally source of benign masses
Gartner's duct cystSEED (Wolffian) derivativesWolffian remnant in ♀ lateral vaginal wall
Round ligament + ovarian lig.GubernaculumTethers ovary → uterus / uterus → labia majora
Key principle: The 2-cell 2-gonadotropin model drives ovarian estrogen — LH on theca → androstenedione → FSH on granulosa (aromatase) → estrogen. After ovulation, the hormonal outputs SWITCH: granulosa lutein → progesterone; theca lutein → estrogen.