female reproductive system

Ovary

Major Functions of the Ovary

The ovaries have two interrelated functions:

• Gametogenesis

  • Production of gametes

• Steroidogenesis

  • Production of steroids

Oogenesis

• In women, production of gametes is called oogenesis.

• Developing gametes are called oocytes.

• Mature gametes are called ova.

Steroid Hormones of the Ovary

Two major groups of steroid hormones are secreted by the ovaries:

• Estrogens

• Progestogens

Estrogens

Estrogens:

• Promote growth and maturation of internal and external sex organs

• Are responsible for female sex characteristics that develop at puberty

• Act on mammary glands to promote breast development by:

  • Stimulating ductal growth

  • Stimulating stromal growth

  • Accumulation of adipose tissue

Progestogens

Progestogens:

• Prepare the internal sex organs, mainly the uterus, for pregnancy

• Promote secretory changes in the endometrium

• Prepare the mammary gland for lactation by promoting lobular proliferation

Role of Both Hormones

Both hormones:

• Play an important role in the menstrual cycle

• Prepare the uterus for implantation of a fertilized ovum

If implantation does not occur:

• Endometrium degenerates

• Menstruation follows

Ovarian Structure

In nulliparas:

• Ovaries are:

  • Paired

  • Almond-shaped

  • Pinkish white structures

Attachments of the Ovary

Mesovarium

• Each ovary is attached to the posterior surface of the broad ligament by a peritoneal fold called the mesovarium.

Superior (Tubal) Pole

• Attached to the pelvic wall by the suspensory ligament of the ovary.

• This ligament carries:

  • Ovarian vessels

  • Nerves

Inferior (Uterine) Pole

• Attached to the uterus by the ovarian ligament.

• Ovarian ligament is a remnant of the gubernaculum.

Gubernaculum

• Embryonic fibrous cord attaching the developing gonad to the floor of the pelvis.

Surface Changes of the Ovary

Before puberty:

• Surface of ovary is smooth

During reproductive life:

• Surface becomes progressively scarred and irregular because of repeated ovulations

In postmenopausal women:

• Ovaries are about one-fourth the size observed during the reproductive period

Regions of the Ovary

The ovary is composed of:

• Cortex

• Medulla

Medulla (Medullary Region)

• Located in the central portion of the ovary

• Contains:

  • Loose connective tissue

  • Relatively large contorted blood vessels

  • Lymphatic vessels

  • Nerves

Cortex (Cortical Region)

• Located in the peripheral portion of the ovary surrounding the medulla

• Contains ovarian follicles embedded in richly cellular connective tissue

• Scattered smooth muscle fibers are present in the stroma around the follicles

Boundary

• Boundary between cortex and medulla is indistinct.

Germinal Epithelium

• Surface of the ovary is covered by:

  • Single layer of cuboidal cells

  • In some parts, almost squamous cells

• This cellular layer is known as the germinal epithelium.

• Germinal epithelium is continuous with the mesothelium covering the mesovarium.

Primordial Germ Cells

• Primordial germ cells:

  • Male and female

  • Are of extragonadal origin

• They migrate:

  • From the embryonic yolk sac

  • Into the cortex of the embryonic gonad

• There they:

  • Differentiate

  • Induce differentiation of the ovary

Tunica Albuginea

• Dense connective tissue layer

• Lies between:

  • Germinal epithelium

  • Underlying cortex

Ovarian Follicles

• Ovarian follicles provide the microenvironment for the developing oocyte.

• Ovarian follicles:

  • Are of various sizes

  • Each contains a single oocyte

  • Are distributed in the stroma of the cortex

• Size of a follicle indicates the developmental state of the oocyte.

Oogenesis During Fetal Life

• Early stages of oogenesis occur during fetal life.

• Mitotic divisions massively increase the number of oogonia.

Oocytes at Birth

• Oocytes present at birth:

  • Remain arrested in development

  • At the first meiotic division

Changes During Puberty

• During puberty:

  • Small groups of follicles undergo cyclic growth and maturation

• First ovulation generally does not take place:

  • For a year or more after menarche

• A cyclic pattern of:

  • Follicular maturation

  • Ovulation

is then established parallel with the menstrual cycle.

Ovulation

• Normally:

  • Only one oocyte reaches full maturity

  • Released from the ovary during each menstrual cycle

• Release of more than one egg at ovulation may lead to multiple zygotes.

Mature Ova

• During reproductive life span:

  • A woman produces only about 400 mature ova.

Atresia

• Most of the estimated 600,000 to 800,000 primary oocytes present at birth:

  • Do not complete maturation

  • Are gradually lost through atresia

Definition of Atresia

• Spontaneous death and subsequent resorption of immature oocytes

Mechanism of Atresia

• Begins as early as the fifth month of fetal life

• Mediated by apoptosis of cells surrounding the oocyte

Effect of Atresia

• Reduces the number of primary oocytes in a logarithmic fashion:

  • From as many as 5 million in the fetus

  • To less than 20% of that number at birth

• Oocytes remaining at menopause degenerate within a few years.

Follicle Development

Histologically, three basic types of ovarian follicles are identified on the basis of developmental state:

• Primordial follicles

• Growing follicles

  • Primary follicles

  • Secondary (antral) follicles

• Mature follicle (Graafian follicle)

Additional Point

• In the cycling ovary, follicles are found at all stages of development.

• Primordial follicles predominate.

Primordial Follicle

General Features

• Earliest stage of follicular development

• First appear during the third month of fetal development

• Early growth is independent of gonadotropin stimulation

Location

• Found in the stroma of the cortex just beneath the tunica albuginea

Structure

• Single layer of squamous follicle cells surrounds the oocyte

• Outer surface of follicle cells is bounded by a basal lamina

• Oocyte and surrounding follicle cells are closely apposed

Oocyte Features

• Measures about 30 µm in diameter

• Has:

  • Large eccentric nucleus

  • Finely dispersed chromatin

  • One or more large nucleoli

Ooplasm

• Cytoplasm of the oocyte is referred to as ooplasm

Balbiani Body

• Ooplasm contains a Balbiani body

At ultrastructural level it is:

• Localized accumulation of:

  • Golgi membranes and vesicles

  • Endoplasmic reticulum

  • Centrioles

  • Numerous mitochondria

  • Lysosomes

Annulate Lamellae

• Human oocytes contain annulate lamellae

• Numerous small vesicles are scattered throughout the cytoplasm with small spherical mitochondria

Annulate lamellae:

• Resemble a stack of nuclear envelope profiles

• Each layer contains pore structures morphologically identical to nuclear pores

Primary Follicle

Definition

• First stage in development of the growing follicle

Changes During Transformation from Primordial to Growing Follicle

Changes occur in:

• Oocyte

• Follicle cells

• Adjacent stroma

Follicle Cell Changes

• Flattened follicle cells proliferate

• Become cuboidal

When follicle cells become cuboidal:

• Follicle is identified as a primary follicle

Zona Pellucida

Formation

• Growing oocyte secretes specific proteins

• Proteins assemble into extracellular coat called zona pellucida

Location

• Appears between:

  • Oocyte

  • Adjacent follicle cells

Zona Pellucida Glycoproteins

Composed of three classes of sulfated acidic zona pellucida glycoproteins:

• ZP-1 (80–120 kDa)

• ZP-2 (73 kDa)

• ZP-3 (59–65 kDa)

Functions

ZP-3

• Most important

• Functions as:

  • Spermatozoa-binding receptor

  • Inducer of acrosome reaction

ZP-2

• Secondary spermatozoa-binding protein

ZP-1

• Not yet functionally characterized

Microscopic Appearance of Zona Pellucida

In light microscope:

• Homogeneous

• Refractile layer

• Stains deeply with:

  • Acidophilic stains

  • PAS reagents

Appearance of Zona Pellucida

• First apparent when:

  • Oocyte surrounded by single layer of cuboidal or columnar follicle cells

  • Oocyte diameter reaches 50–80 µm

Granulosa Layer Formation

Stratification of Follicle Cells

• Rapid mitotic proliferation converts single layer into stratified epithelium called:

  • Membrana granulosa

  • Stratum granulosum

Granulosa Cells

• Follicle cells are now called granulosa cells

Basal Lamina

• Remains between:

  • Outermost follicle cells

  • Connective tissue stroma

Gap Junctions

• Extensive gap junctions develop between granulosa cells

Blood–Follicle Barrier

• Basal layer of granulosa cells lacks elaborate tight junctions (zonulae occludentes)

• Indicates absence of blood–follicle barrier

Follicular Nutrition

• Movement of nutrients and small informational macromolecules from blood into follicular fluid is essential for normal development of ovum and follicle

Theca Layers

Formation

• Stromal cells surrounding follicle form sheath of connective tissue cells called theca folliculi

Theca Interna

Features

• Inner highly vascularized layer

• Made of cuboidal secretory cells

Ultrastructural Features

• Characteristic of steroid-producing cells

LH Receptors

• Cells possess many luteinizing hormone (LH) receptors

Function

In response to LH stimulation:

• Synthesize and secrete androgens

• Androgens are precursors of estrogens

Additional Components

Contains:

• Fibroblasts

• Collagen bundles

• Rich network of small vessels typical of endocrine organs

Theca Externa

• Outer layer of connective tissue cells

• Contains mainly:

  • Smooth muscle cells

  • Bundles of collagen fibers

Boundaries

• Boundaries between thecal layers and surrounding stroma are not distinct

Function of Basal Lamina

• Basal lamina between granulosa layer and theca interna forms distinct boundary

• Separates:

  • Rich capillary bed of theca interna

  • Avascular granulosa layer during follicular growth

Oocyte Maturation in Primary Follicle

Cytoplasmic Changes

As oocyte matures:

• Organelles redistribute

Changes Seen

Increase in:

• Free ribosomes

• Mitochondria

• Small vesicles

• Multivesicular bodies

• Rough-surfaced ER

May also contain:

• Lipid droplets

• Lipchrome pigment masses

Cortical Granules

• Specialized secretory vesicles

• Located beneath oolemma

Oolemma

• Plasma membrane of oocyte

Function of Cortical Granules

Contain proteases released by exocytosis when ovum is activated by sperm

Perivitelline Space

• Numerous irregular microvilli project from oocyte into perivitelline space

Granulosa Cell Processes

• Slender processes from granulosa cells:

  • Project toward oocyte

  • Intermingle with oocyte microvilli

  • Occasionally invaginate into oocyte plasma membrane

• Processes may contact plasma membrane but do not establish cytoplasmic continuity

Secondary (Antral) Follicle

Characteristic Feature

• Presence of fluid-containing antrum

Growth of Primary Follicle

• Moves deeper into cortical stroma as size increases

• Mainly through proliferation of granulosa cells

Factors Required for Growth

• Follicle-stimulating hormone (FSH)

• Growth factors

  • Epidermal growth factor (EGF)

  • Insulin-like growth factor I (IGF-I)

• Calcium ions (Ca²⁺)

Formation of Fluid-Filled Cavities

• When stratum granulosum reaches 6–12 cell layers:

  • Fluid-filled cavities appear among granulosa cells

Liquor Folliculi

• Hyaluronan-rich fluid accumulating among granulosa cells

Antrum Formation

• Cavities coalesce forming:

  • Single crescent-shaped cavity called antrum

Secondary / Antral Follicle

• Follicle now identified as:

  • Secondary follicle

  • Antral follicle

Oocyte in Secondary Follicle

• Eccentrically positioned

• Diameter about 125 µm

• Undergoes no further growth

Oocyte Maturation Inhibitor (OMI)

• Small peptide of 1–2 kDa

• Secreted by granulosa cells into antral fluid

Function of OMI

• Inhibits oocyte growth

Correlation of OMI

• Direct correlation exists between:

  • Size of secondary follicle

  • OMI concentration

• OMI concentration:

  • Highest in small follicles

  • Lowest in mature follicles.

Cumulus Oophorus and Corona Radiata

Changes in the Secondary Follicle

• As the secondary follicle increases in size:

  • The antrum enlarges

  • The antrum is lined by several layers of granulosa cells

• Stratum granulosum has relatively uniform thickness except in the region associated with the oocyte.

Cumulus Oophorus

• Granulosa cells form a thickened mound called the cumulus oophorus.

• Cumulus oophorus projects into the antrum.

Corona Radiata

• Cells of the cumulus oophorus immediately surrounding the oocyte and remaining with it at ovulation are called the corona radiata.

Structure of Corona Radiata

• Composed of cumulus cells

• These cells send penetrating microvilli throughout the zona pellucida

• Communicate via gap junctions with microvilli of the oocyte

Changes During Follicular Maturation

• Number of surface microvilli of granulosa cells increases

• Correlated with increased number of LH receptors on the free antral surface

Call-Exner Bodies

• Extracellular

• Densely staining

• PAS-positive material

Called:

• Call-Exner bodies

Origin and Contents

• Secreted by granulosa cells

• Contain:

  • Hyaluronan

  • Proteoglycans

Mature (Graafian) Follicle

Definition

• Mature follicle is also known as Graafian follicle.

Features

• Diameter of 10 mm or more

• Extends through full thickness of ovarian cortex

• Causes bulge on surface of ovary

Changes Near Maximum Size

• Mitotic activity of granulosa cells decreases

• Stratum granulosum becomes thinner as antrum enlarges

Changes Before Ovulation

• Spaces between granulosa cells enlarge

• Oocyte and cumulus cells become gradually loosened from remaining granulosa cells

Purpose:

• Preparation for ovulation

Corona Radiata in Mature Follicle

• Cumulus cells immediately surrounding oocyte form a single layer called corona radiata.

• These cells and loosely attached cumulus cells remain with the oocyte at ovulation.

Changes in Thecal Layers

During follicle maturation:

• Thecal layers become more prominent

Theca Interna Cells

• Lipid droplets appear in cytoplasm

• Cells show ultrastructural features associated with steroid-producing cells

Hormonal Activity

LH Action

• LH stimulates theca interna cells to secrete androgens.

Aromatase

• Theca interna cells lack the enzyme aromatase.

• Therefore, they cannot produce estrogens.

Granulosa Cells

• Granulosa cells contain aromatase.

• Some androgens are transported to smooth-surfaced ER for further processing.

FSH Action

In response to FSH:

• Granulosa cells convert androgens to estrogens

Effects:

• Stimulates granulosa cell proliferation

• Increases size of follicle

Estrogen Levels

• Increased estrogen levels from:

  • Follicular sources

  • Systemic sources

are correlated with increased sensitization of gonadotropes to gonadotropin-releasing hormone.

Hormonal Surge Before Ovulation

• Surge of FSH or LH occurs in adenohypophysis approximately 24 hours before ovulation.

Effects of LH Surge

• LH receptors on granulosa cells become downregulated (desensitized)

• Granulosa cells no longer produce estrogens in response to LH

Meiotic Division

• LH surge triggers resumption of first meiotic division of the primary oocyte

Occurs:

• Between 12 and 24 hours after LH surge

Results in formation of:

• Secondary oocyte

• First polar body

Luteinization

• Granulosa cells and thecal cells undergo luteinization

• Produce progesterone.

Ovulation

Definition

• Ovulation is a hormone-mediated process resulting in the release of the secondary oocyte.

• Ovulation is the process by which a secondary oocyte is released from the Graafian follicle.

Follicle Selection

• Follicle destined to ovulate in a menstrual cycle is recruited from a cohort of several primary follicles in the first few days of the cycle.

During Ovulation

• Oocyte traverses the entire follicular wall, including the germinal epithelium.

Factors Responsible for Release of the Secondary Oocyte

Release occurs in the middle of the menstrual cycle:

• Day 14 of a 28-day cycle

Factors include:

• Increase in volume and pressure of follicular fluid

• Enzymatic proteolysis of follicular wall by activated plasminogen

• Hormonally directed deposition of glycosaminoglycans between:

  • Oocyte–cumulus complex

  • Stratum granulosum

• Contraction of smooth muscle fibers in the theca externa layer triggered by prostaglandins

Macula Pellucida / Follicular Stigma

• Just before ovulation:

  • Blood flow stops in a small area of ovarian surface overlying the bulging follicle

• Area of germinal epithelium becomes:

  • Elevated

  • Then ruptures

This area is called:

• Macula pellucida

• Follicular stigma

Release of the Oocyte

• Oocyte surrounded by:

  • Corona radiata

  • Cells of cumulus oophorus

is released from the ruptured follicle.

Role of Fimbriae

• At ovulation, fimbriae of uterine tube become closely apposed to surface of ovary.

• Cumulus mass containing oocyte is swept by fimbriae into:

  • Abdominal ostium of uterine tube

Transport in Uterine Tube

• Cumulus mass firmly adheres to fimbriae

• Actively transported by ciliated cells lining uterine tube

• Prevents passage into peritoneal cavity

Primary Oocyte Arrest

Important Point

• Primary oocyte is arrested for 12 to 50 years in the diplotene stage of prophase of the first meiotic division.

Meiotic Arrest

• Primary oocytes within primordial follicles begin first meiotic division in embryo.

• Process becomes arrested at:

  • Diplotene stage of meiotic prophase

• First meiotic prophase is not completed until just before ovulation.

Duration of Arrest

• Primary oocytes remain arrested in first meiotic prophase for 12 to 50 years.

Completion of First Meiotic Division

• First meiotic division (reduction division) is completed in the mature follicle.

Daughter Cells

• Each daughter cell receives equal share of chromatin.

Secondary Oocyte

• One daughter cell receives most of cytoplasm

• Becomes secondary oocyte

• Measures 150 µm in diameter

First Polar Body

• Other daughter cell receives minimal amount of cytoplasm

• Becomes first polar body

Secondary Oocyte

Meiotic Arrest

• Secondary oocyte is arrested at metaphase in the second meiotic division just before ovulation.

Second Meiotic Division

• As soon as first meiotic division is completed:

  • Secondary oocyte begins second meiotic division

• During ovulation:

  • Secondary oocyte surrounded by corona radiata leaves the follicle

  • Second meiotic division is in progress

Arrest at Metaphase

• Second meiotic division is arrested at metaphase.

• Division is completed only if:

  • Secondary oocyte is penetrated by a spermatozoon

If Fertilization Occurs

• Secondary oocyte completes second meiotic division

• Forms:

  • Mature ovum

  • Maternal pronucleus containing 23 chromosomes

Second Polar Body

• Other cell produced during second meiotic division is the second polar body.

First Polar Body in Humans

• First polar body persists for more than 20 hours after ovulation

• Does not divide

Recognition of Fertilized Egg

Fertilized egg can be recognized by presence of:

• Diploid first polar body

• Haploid second polar body.

• Before ovulation → meiosis I completes

• During ovulation → meiosis II is ongoing

• After ovulation → arrested at metaphase II

• After fertilization → meiosis II completes + second polar body appears.

Corpus Luteum — Simple Explanation

After ovulation, the ruptured Graafian follicle changes into the corpus luteum.

What Happens After Ovulation

1. Follicular wall collapses

• The empty follicle shrinks and folds inward after the oocyte leaves.

2. Bleeding occurs

• Capillaries in the theca interna rupture.

• Blood enters the follicle cavity.

This temporary blood-filled structure is called:

• Corpus hemorrhagicum

3. Connective tissue invasion

• Connective tissue from ovarian stroma enters the follicular cavity.

Luteinization

Meaning

Granulosa cells and theca interna cells transform into luteal cells.

During luteinization cells:

• Increase in size

• Fill with lipid droplets

• Accumulate lipochrome pigment

This gives the corpus luteum its yellow color (“luteum” = yellow).

Ultrastructure of Steroid-Secreting Cells (TEM)

These luteal cells are active steroid-producing cells, so they contain:

• Abundant smooth ER (sER)

• Mitochondria with tubular cristae

These are classic features of steroid hormone synthesis.

Granulosa Lutein Cells

Derived from:

• Granulosa cells

Features:

• Large cells

• About 80% of corpus luteum

Function:

• Synthesize:

  • Estrogens

  • Progesterone

  • Inhibin

Theca Lutein Cells

Derived from:

• Theca interna cells

Features:

• Smaller

• Darker

• About 20% of cells

Function:

• Secrete:

  • Androgens

  • Progesterone

Vascularization

• Blood vessels grow into the corpus luteum from the theca interna.

• This increases blood supply for hormone secretion.

CORPUS LUTEUM

Corpus luteum of menstruation

• Forms after ovulation when fertilization does not occur.

• In the absence of human chorionic gonadotropin (hCG), the corpus luteum cannot be maintained.

Important:

• The corpus luteum remains active for only 14 days.

Degeneration of corpus luteum

• After about 14 days, it starts to degenerate.

• Degeneration causes a decline in estrogen and progesterone levels.

Why is this important?

• Normally, estrogen and progesterone inhibit the secretion of LH and FSH through negative feedback.

• When estrogen and progesterone decrease, this inhibition is removed.

• As a result:

  • LH and FSH levels rise again

  • A new ovarian cycle can begin.

MOST IMPORTANT POINT

• No hCG → corpus luteum degenerates after 14 days → estrogen & progesterone decrease → LH and FSH inhibition removed → new menstrual cycle starts.

Corpus luteum of pregnancy

• Forms when fertilization and implantation occur.

• During pregnancy, the corpus luteum is maintained instead of degenerating.

Size

• It increases in size and becomes about 2–3 cm.

Depends on luteotropins

Luteotropins are substances that support and maintain the corpus luteum.

1. Paracrine luteotropins

(Act locally within the ovary)

Include:

• Estrogens

• IGF-I and IGF-II (Insulin-like Growth Factors)

Function:

• Help maintain luteal cell activity.

• Support hormone production by the corpus luteum.

2. Endocrine luteotropins

(Act through the bloodstream)

Include:

• hCG

• LH and prolactin

• Insulin

Important role of hCG

• hCG is the main hormone responsible for maintaining the corpus luteum during pregnancy.

• hCG is produced by the developing embryo/trophoblast after implantation.

Progesterone production

• The corpus luteum of pregnancy produces high levels of progesterone.

Function of progesterone

• Prevents cyclic development of new ovarian follicles.

• Maintains the endometrium for pregnancy.

• Helps prevent menstruation during pregnancy.

MOST IMPORTANT POINT

• High progesterone from the corpus luteum prevents development of new ovarian follicles during pregnancy.

Decline of corpus luteum

• The corpus luteum begins to decline gradually after 8 weeks of pregnancy.

Why?

• Because the placenta starts producing sufficient progesterone.

• Therefore, the corpus luteum is no longer the main source of progesterone.

MOST IMPORTANT POINT

• After ~8 weeks, the placenta takes over progesterone production, so the corpus luteum gradually regresses.

FOLLICLE ATRESIA

Ovarian follicular atresia

• Follicular atresia = degeneration and loss of ovarian follicles that do not complete maturation.

• It is a normal physiologic process in the ovary.

Can occur during:

• Embryonic life

• Fetal life

• Early postnatal life

• Puberty

• Reproductive years

Important:

• Atresia can occur at any stage of follicle maturation.

Main mechanism

• Follicular atresia is mainly mediated by apoptosis of granulosa cells.

Apoptosis

= programmed cell death.

Why granulosa cells are important:

• Granulosa cells support:

  • nourishment of the oocyte

  • follicular growth

  • hormone production

So when granulosa cells undergo apoptosis, the follicle cannot survive.

MOST IMPORTANT POINT

• Apoptosis of granulosa cells is the key initiating event in follicular atresia.

Fate of follicles during atresia

Small follicles

• Small follicles:

  • shrink

  • gradually degenerate

  • eventually disappear completely

Large follicles

• Large follicles form a:

  • scar with hyaline streaks

Hyaline streaks

= eosinophilic, glassy scar-like material left after degeneration.

• Later, this scar disappears because:

  • the ovarian stroma invades the area

I. Degenerative changes in the follicular wall

1. Initiation of apoptosis within granulosa cells + hydrolytic enzymes

• Granulosa cells begin programmed cell death.

• Hydrolytic enzymes help break down follicular structures.

Result:

• Destruction of the follicular wall.

2. Invasion of granulosa layer by neutrophils and macrophages

• Inflammatory cells enter the degenerating follicle.

Neutrophils

• participate in tissue breakdown.

Macrophages

• remove cellular debris by phagocytosis.

3. Vascularization

• Blood vessels grow into the degenerating follicle.

Purpose:

• Helps removal of degenerated tissue.

• Supports repair/remodeling process.

4. Hypertrophy of the theca interna cells

Hypertrophy

= increase in cell size.

• Theca interna cells enlarge during atresia.

Why?

• These cells may continue temporary steroid production.

5. Collapse of the follicle

• As degeneration progresses:

  • follicular fluid decreases

  • follicular structure collapses

6. Invasion of connective tissue

• Connective tissue enters the collapsed follicle.

Result:

• Fibrosis/scarring develops.

II. Oocyte degeneration

1. Autolysis + macrophage phagocytosis

Autolysis

= self-digestion of the oocyte by its own enzymes.

• Macrophages then phagocytose the remaining debris.

2. Zona pellucida folding

• The zona pellucida becomes folded and irregular during degeneration.

Why?

• Because the oocyte shrinks and degenerates.

III. Basement membrane changes

Basement membrane

• becomes:

  • thickened

  • wavy

  • glassy in appearance

This forms the:

• glassy membrane

MOST IMPORTANT POINT

• Thickened wavy basement membrane = glassy membrane, which is characteristic of follicular atresia.

HIGH-YIELD SUMMARY

Key sequence of follicular atresia:

1. Granulosa cell apoptosis

2. Degeneration of follicular wall

3. Macrophage/neutrophil invasion

4. Oocyte degeneration

5. Follicle collapse

6. Connective tissue invasion and scar formation

7. Formation of thick glassy membrane

MOST IMPORTANT EXAM POINTS

• Atresia can occur at any stage of follicle maturation

• Granulosa cell apoptosis initiates atresia

• Large follicles form hyaline scar tissue

• Characteristic glassy membrane develops from thickened basement membrane

UTERINE TUBES

General features

• Uterine tubes are hollow organs that extend from the uterus toward the ovaries.

• Also called:

  • Fallopian tubes

  • Oviducts

Functions of uterine tubes

1. Transport of the ovum

• The uterine tubes transport the ovum from the ovary to the uterus.

How transport occurs:

• By:

  • ciliary movement

  • smooth muscle contraction (peristalsis)

2. Site/environment for fertilization

• The uterine tube provides the proper environment for:

  • fertilization

  • early development of the zygote

MOST IMPORTANT POINT

• Fertilization usually occurs in the ampulla of the uterine tube.

Parts of the uterine tube

The uterine tube is divided into 4 parts:

1. Intramural part

2. Isthmus

3. Ampulla

4. Infundibulum

1. Intramural part

Definition

• The proximal portion of the uterine tube that enters the wall of the uterus.

Proximal

= closer to the uterus/origin.

Important:

• This segment passes through the uterine wall.

2. Isthmus

Definition

• Narrow, medial segment adjacent to the uterus.

Features

• Short

• Narrow lumen

• Thick muscular wall

Medial

= closer to the midline/uterus.

3. Ampulla

Definition

• The longest segment of the uterine tube.

Features

• Wider lumen

• More tortuous (curved)

MOST IMPORTANT POINT

• Ampulla is the usual site of fertilization.

4. Infundibulum

Definition

• Distal funnel-shaped portion of the uterine tube.

Distal

= farther from the uterus.

Fimbriae

• The infundibulum has:

  • ciliated fingerlike projections called fimbriae

Function of fimbriae

• They drape over the ovary.

• Help capture the ovulated oocyte and guide it into the uterine tube.

Cilia

• Move the oocyte toward the uterus.

MOST IMPORTANT POINT

• Fimbriae help pick up the ovulated oocyte from the ovary.

Sequence from uterus to ovary

From medial → lateral:

1. Intramural part

2. Isthmus

3. Ampulla

4. Infundibulum with fimbriae.

1. Serosa

Outermost layer.

Composition

• Mesothelium

• Thin connective tissue

Also called

• Peritoneum

2. Muscularis

Smooth muscle layer.

Arrangement

• Inner thick circular layer

• Outer thin longitudinal layer

Important

• Boundary between layers may be indistinct

Function of Muscularis

• Peristaltic contractions

• Transport of ovum/zygote

3. Mucosa

Inner lining.

Features

• Thin longitudinal folds projecting into lumen

• Folds present throughout tube

Most numerous and complex in

• Ampulla

Smaller in

• Isthmus

Mucosal Components

A. Lamina Propria

• Loose connective tissue

B. Epithelium

Type

• Simple columnar epithelium

Two cell types

1. Ciliated cells

2. Nonciliated peg cells

Ciliated Cells

Location

Most numerous in:

• Infundibulum

• Ampulla

Function

• Ciliary movement directed toward uterus

• Move ovum toward uterus

Nonciliated Peg Cells

Type

• Secretory cells

Function

• Produce nutritive fluid for ovum

Hormonal Changes

Estrogen

• Stimulates ciliogenesis

• Increases ciliated cells

Progesterone

• Increases secretory (peg) cells

Cyclic Changes

• Epithelium hypertrophies during follicular phase

• Atrophies during luteal phase

• Ratio of ciliated to secretory cells changes during cycle

Transport in Uterine Tube

Mechanisms

1. Ciliary movement

2. Peristaltic muscular contractions

Fertilization

Usually occurs

• In the ampulla

• Near junction with isthmus.

ENDOMETRIUM & MENSTRUAL CYCLE — EXAM NOTES

Endometrium

• Mucosa of the uterus

• Undergoes cyclic monthly changes during reproductive life

• Changes prepare uterus for:

  • implantation

  • embryonic development

  • fetal development

Endometrial Changes

• Correlated with maturation of ovarian follicles

• Secretory activity changes during cycle

Menstruation (Menstrual Flow)

Definition

• Partial destruction and sloughing of endometrium

• Accompanied by bleeding from mucosal vessels

Menstrual Flow

• Discharge of blood and tissue through vagina

• Usually lasts 3–5 days

Menstrual Cycle

Definition

• Begins on the first day of menstrual flow

Layers of the Endometrium

The endometrium has 2 layers:

1. Stratum functionale

2. Stratum basale

1. Stratum Functionale (Functional Layer)

Features

• Thick superficial layer

• Undergoes cyclic changes

Important

• Sloughed off during menstruation

2. Stratum Basale (Basal Layer)

Features

• Deep layer

• Remains after menstruation

Function

• Regenerates the stratum functionale.

BLOOD SUPPLY OF THE ENDOM

This diagram shows how blood reaches the endometrium and why menstruation occurs.

The arteries branch in a very specific order.

Sequence of Arteries

1. Uterine Artery

Main artery supplying the uterus.

↓

2. Arcuate Arteries

• Usually 6–10

• Run within the myometrium

• Course circumferentially around uterus

↓

3. Radial Arteries

• Branch from arcuate arteries

• Enter the endometrium from the myometrium

• Reach the basal layer (stratum basale)

↓

At this point the vessels divide into:

A. Straight Arteries

B. Spiral Arteries

Straight Arteries

Supply

• Stratum basale (basal layer)

Important

• Relatively stable

• Do NOT undergo cyclic degeneration

Function

• Maintain blood supply to basal layer

• Allow regeneration after menstruation

Spiral (Coiled) Arteries

Supply

• Stratum functionale (functional layer)

Features

• Long

• Coiled/spiral shape

• Extend toward surface epithelium

Branches

• Arterioles

• Rich capillary bed

Lacunae / Venous Sinusoids

The capillaries form:

• dilated vascular spaces

Called:

• lacunae

• venous sinusoids

These help nourish the functional layer.

Most Important Concept

Distal portion of spiral arteries:

• Undergoes cyclic degeneration and regeneration

This is the key event in menstruation.

CYCLIC CHANGES OF ENDOMETRIUM — EXAM NOTES

Menstrual Cycle

• Cyclic changes occur in the functional layer of endometrium

• Controlled by:

  • pituitary gonadotropins

  • ovarian hormones

Normal duration

• About 28 days

Three Phases of Menstrual Cycle

1. Proliferative phase

2. Secretory phase

3. Menstrual phase

1. PROLIFERATIVE PHASE

Hormone

• Regulated by estrogen

Occurs with

• Follicular maturation

• Begins after menstruation

Endometrium at Beginning

After menstruation:

• Endometrium thin

• About 1 mm thick

• Contains:

  • stratum basale

  • basal portions of glands

  • lower portions of spiral arteries

Changes During Proliferative Phase

Epithelium

• Rapid proliferation of:

  • stromal cells

  • endothelial cells

  • epithelial cells

Uterine Glands

• Reconstituted from basal portions

• Cells migrate to cover surface

• Glands:

  • narrow lumen

  • relatively straight

  • may appear slightly wavy

Stroma

• Stromal cells proliferate

• Produce:

  • collagen

  • ground substance

Spiral Arteries

• Lengthen as endometrium thickens

• Slightly coiled

• Extend into upper third of endometrium

End of Proliferative Phase

Time

• Around day 14 (ovulation)

Endometrial thickness

• About 3 mm

Glycogen

• Present in basal epithelial cytoplasm

• Appears as empty spaces in routine histology

High-Yield Histology of Proliferative Phase

2. SECRETORY PHASE

Hormone

• Regulated by progesterone

Occurs with

• Corpus luteum activity

Begins

• 1–2 days after ovulation

Changes During Secretory Phase

Endometrium

• Becomes edematous

• May reach 5–6 mm thickness

Glands

• Enlarge

• Become corkscrew-shaped

• Lumen becomes sacculated

• Filled with secretory product

Secretions

Rich in:

• glycogen

• nutrients

Function

• Support implantation

Spiral Arteries

• Lengthen further

• Become more coiled

• Extend near surface

Stromal Cells

Under estrogen + progesterone influence:

• transform into decidual cells

Decidual Cells

• Rich in glycogen

• Support nourishment of embryo

High-Yield Histology of Secretory Phase

3. MENSTRUAL PHASE

Cause

• Decline of:

  • progesterone

  • estrogen

Due to

• Degeneration of corpus luteum

Initial Event

• Periodic contraction of spiral arteries

↓

• Ischemia of stratum functionale

↓

• Degeneration and shrinkage of endometrium

Further Changes

Prolonged arterial contraction causes:

• Rupture of vessels

• Surface epithelium disruption

Menstrual Discharge Contains

• Blood

• Uterine fluid

• Stromal cells

• Epithelial cells

• Tissue fragments

During Menstruation

• Stratum functionale sloughs off

• Only stratum basale remains

Blood Supply During Menstruation

• Spiral arteries degenerate

• Straight arteries maintain basal layer

Menstrual Flow

Duration

• About 5 days

Average blood loss

• 35–50 mL

Histology of Menstrual Phase

Anovulatory Cycle

Definition

• Cycle without ovulation

Important

• No corpus luteum forms

• No progesterone produced

Result

• Endometrium does NOT enter secretory phase

• Remains in proliferative phase until menstruation

PLACENTA — EXAM NOTES

Placenta

• Organ maintaining developing fetus

• Formed from:

  • fetal tissues

  • maternal tissues

Components of Placenta

Fetal Portion

• Formed by chorion

Maternal Portion

• Formed by decidua basalis

Function

• Physiologic exchange between:

  • maternal circulation

  • fetal circulation

Uteroplacental Circulatory System

Begins

• Around day 9

Trophoblastic Lacunae

• Vascular spaces within syncytiotrophoblast

Maternal Sinusoids

• Develop from maternal capillaries

• Anastomose with trophoblastic lacunae

Result

• Primitive uteroplacental circulation established

Syncytiotrophoblast

Contains:

• numerous pinocytotic vesicles

Function

• Transfer nutrients from mother to embryo

Chorionic Villi Development

Develop by:

1. Cytotrophoblast proliferation

2. Growth of chorionic mesoderm

3. Blood vessel developmen

TYPES OF CHORIONIC VILLI

1. Primary Chorionic Villi

Formation

• Rapid proliferation of cytotrophoblast

Structure

• Cytotrophoblastic cords covered by syncytiotrophoblast

Appear

• Days 11–13

2. Secondary Chorionic Villi

Formation

• Primary villi invaded by loose connective tissue from chorionic mesenchyme

Structure

• Central mesenchymal core

• Inner cytotrophoblast

• Outer syncytiotrophoblast

Develop

• Around day 16

3. Tertiary Chorionic Villi

Formation

• Secondary villi become vascularized

Feature

• Blood vessels develop within connective tissue core

Time

• End of 3rd week

Trophoblastic Shell

Formation

• Cytotrophoblast cells grow through syncytiotrophoblast

• Reach maternal endometrium

• Grow laterally and fuse

Result

• Thin outer cytotrophoblastic layer

Chorionic Villi Types

Floating Villi

• Free within intervillous space

Stem (Anchoring) Villi

• Attach to maternal side (basal plate)

Placental Growth

• Occurs by interstitial growth of trophoblastic shell

Changes During Pregnancy

Chorionic Villi

• Become smaller in diameter with maturation

Cytotrophoblast

• Appears discontinuous in mature villi

Syncytial Knots

Definition

• Clusters of syncytiotrophoblast nuclei

Importance

• Increase with gestational age

• Indicator of villous maturity

Increased Syncytial Knots Associated With

• Uteroplacental malperfusion

Cells in Villous Stroma

Recognized cells include:

• Mesenchymal cells

• Reticular cells

• Fibroblasts

• Myofibroblasts

• Smooth muscle cells

• Placental macrophages

Hofbauer Cells

Also called

• Fetal placental antigen-presenting cells

• Placental macrophages

Origin

• Fetal origin

Function

• Participate in placental innate immune reactions

• Antigen presentation

Features of Hofbauer Cells

• Increase MHC II molecules when stimulated

• More common in early placenta

• Vacuoles contain:

  • lipids

  • glycosaminoglycans

  • glycoproteins

HIV Infection

• HIV may localize in:

  • Hofbauer cells

  • syncytiotrophoblast