Ovarian structures and function

Structures on the Ovaries and Their Function

• Ovaries – Characterized as an organ of constant change

• A series of dynamic changes in a very predictable manner during the reproductive cycle.

• Cyclic changes – Development of large fluid-

filled structures called follicles

– Rupture of the ovulatory follicle and release of the oocyte (ovulation)

– Formation of a corpus luteum from remnants of the ovulated follicle.

• Destruction of the corpus luteum (CL) – Prostaglandin F2alpha (PGF2)

near the end of the cycle if pregnancy is not initiated

– Demise of the CL• Development of an ovulatory

follicle and release of the oocyte at ovulation

• Series of events takes place in the predictable manner– Once every three weeks in

cows– Once every four weeks in

humans

Association between cyclic changes in ovarian structures and hormone

production• Production of two steroid hormones

(Estradiol and Progesterone) – Key regulators of the reproductive cycle,

reproductive behavior, and maintenance of pregnancy

Sections of Ovaries

• Two distinct regions.– cortex (outer)

– medulla (inner)

Medulla

Cortex

Ovarian Cortex

• The ovarian cortex – The outer region of the

ovary. – Covered by a layer of

connective tissue called the tunica albuginea

• No ability to produce estradiol or progesterone

• Does not contain oocytes

Medulla

Cortex

Ovarian Cortex

• Follicles – Eventually grow and

become capable of undergoing ovulation

• The CL• Cells/tissues

responsible for production of estradiol and progesterone

Medulla

Cortex

Ovarian Medulla

• The ovarian medulla – The central area of the

ovary

– Made of dense connective tissues

– Contains blood vessels, nerves, and lymph ducts.

Medulla

Cortex

Structures within the ovarian cortex

• Follicles– Five (5) different types present in the ovarian cortex at any given period of time during

the reproductive cycle• Primordial• Primary• Secondary• Tertiary• Antral

Follicles

• Primordial, primary, and secondary follicles – Often referred to as preantral

follicles– Microscopic in size– Classified individually

(primordial versus primary versus secondary) based upon cell shape (flat vs. cube) and number of cell layers (one vs. multiple) surrounding the oocyte

Primodial

Primary

Secondary

Preantral follicles

Primodial PrimarySecondary

Follicles

• Antral follicles – have a hollow fluid-filled

cavity • An antrum. • Less pronounced in

developing tertiary follicles.

– The fluid within the antrum • Follicular fluid

– Size of antral follicles varies depending on the stage of follicular development

• Some antral follicles (> 1 mm) are visible on the surface of the ovary as blister-like structures

Antral follicles

Antral follicles

Antral follicles

Follicles• The wall of a follicle

– Composed of three distinct cell layers

• The inner most layer (facing the antrum)

– Granulosa cells

• The second layer of cells– Theca interna

• The outer most layer (facing ovarian cortex)

– theca externa

– Theca interna and theca externa • Theca cells

– Granulosa cell layer is separated from theca cell layer by a thin membrane called a basement membrane.

Antrum

Granulosa cells

Theca internaTheca externa

Basementmembrane

Oocyte

Follicles

• Both theca and granulosa cells are involved in production of estradiol– Theca cells produce androgens

– Granulosa cells convert androgens to estradiol

• Granulosa cells – Nurse cells by producing

• Numerous materials essential for development of the oocyte

Luteal structures

• After ovulation– The oocyte is released from the preovulatory follicle

– Theca and granulosa cells remaining in the follicular wall undergo dramatic changes

• Formation of a corpus luteum.

– A shift from producing estradiol (granulosa) and androgen (theca) to producing large amounts of progesterone

Luteal structures

• Three structures – Corpus hemorrhagicum (CH)

– Corpus Luteum (CL)

– Corpus Albicans (CA)

• These names refer to the same structure (luteal) but with differing features characteristic of different stages of the reproductive cycle

Luteal structures• The corpus hemorrhagicum

(bloody body)– During the early part of the luteal

phase of the reproductive cycle

– Appears red • Small blood vessels within the

follicle rupture during ovulation

• Collapse of follicular wall into many folds after leakage of follicular fluid into many folds

CH

CH

Early CHDeveloping CH

Luteal structures

• The corpus luteum (yellow body)– Found during the middle

part of the luteal phase of the reproductive cycle

– The major source of progesterone

– Some have a CL with a very large fluid-filled cavity, whereas others have a CL without a distinguishable cavity

CL

CL

CL withcavity

CL withoutcavity

Luteal structures

• The corpus albicans (white body)– A white, fibrous tissue– Remains of the CL

• Loss of ability to produce progesterone

• Death of cells in the CL– It eventually

completely loses the ability to produce progesterone

– Leads to follicular phase

CA

CA

Early CA

Advanced CA

Pattern of follicular development and changes in blood hormone

concentrations• Secondary FSH surge

– Immediately after ovulation– A group of small (3 to 4 mm

in diameter) antral follicles (cohort) begins to grow as FSH concentrations peak

• Emergence• Follicles continue to grow in

size and produce estradiol as blood concentrations of FSH begin to decline

Ovulation

FSH

E2

Pattern of follicular development and changes in blood hormone

concentrations• Decrease in blood

FSH – Partly caused by

increased estradiol concentrations in the blood

• Negative feedback.

Ovulation

FSH

Estradiol

Pattern of follicular development and changes in blood hormone

concentrations• Decline in blood FSH

concentrations– Some of the follicles within a

cohort stop growing and begin to die at this stage

• Atresia

– A few follicles within the cohort continue to grow as FSH concentrations approach baseline

• Growth rate slows down rapidly for all but one of these follicles

Ovulation

FSH

Pattern of follicular development and changes in blood hormone

concentrations• The follicle that is bigger

than the rest of group when FSH concentrations reach baseline– The dominant follicle

• The rest of follicles within the cohort – Subordinate follicles

• The time point, in which the dominant follicle begins to grow faster than subordinate follicles– Deviation.

Dominant Follicle

Ovulation

FSH

Subordinate Follicles

Deviation

Pattern of follicular development and changes in blood hormone

concentrations

• The dominant follicle – continues to grow even though blood

concentrations of FSH are low

• Subordinate follicles stop growing and undergo atresia

• Growth of the dominant follicle under low blood FSH – Achieved by acquisition of LH

receptors on the granulosa cells and a shift to LH responsiveness

– Produces a large amount of estradiol, and blood concentrations of estradiol increase.

+ +

LH

+

Ovulation

FSH

Pattern of follicular development and changes in blood hormone

concentrations• Increase in blood estradiol

– No preovulatory LH surge and ovulation

• The newly formed CL – Producing progesterone as

it begins to grow at the same time

– Progesterone inhibits preovulatory surges of GnRH and LH (this is also negative feedback).

LH+ ++

CL

P4

(-)

Pattern of follicular development and changes in blood hormone

concentrations• The dominant follicle

– Eventually reaches a size similar to that of the preovulatory follicle (growth plateau)

– Stops growing but actively produces estradiol

– Lack of hormonal support• The dominant follicle eventually

stops producing estradiol and begins to undergo atresia (loss of dominance).

+ +

LH

+

Pattern of follicular development and changes in blood hormone

concentrations• Decreased estradiol

production by the dominant follicle– Removal of the negative

feedback on FSH

– Blood FSH concentrations begin to increase

– A new cohort of antral follicles begin to grow in the ovary

• The whole process, therefore, is repeated.

+ +

LH

+

Pattern of follicular development and changes in blood hormone

concentrations

• The pattern of follicular development in human and cattle resembles that of a wave (follicular wave)– One cohort of follicles emerges in the beginning

– One of the follicles within the cohort becomes the dominant follicle and continues to grow

– After reaching its growth plateau, the dominant follicle begins to shrink, and a new cohort emerges shortly thereafter

Ovulation

CH

CL

Ovulation

C

Adapted from Lucy et al., 1992

Ovulation Ovulation

Pattern of follicular development and changes in blood hormone

concentrations

• During the reproductive cycle, females may develop two or three follicular waves, with the dominant follicle that develops during the last wave being the ovulatory follicle

CL

Ovulation

CH

Ovulation

CHOvulation

Adapted from Lucy et al., 1992

Two Waves

Three Waves

OvulationOvulation

Ovulation Ovulation

Ovulation

• The process by which the ovarian follicle physically ruptures– Release of the oocyte

– Transformation of follicular cells (theca and granulosa cells) into luteal cells

• Factors involved in rupture of the preovulatory follicle– Build-up of the fluid

pressure within the follicle

– Thinning of the cell layers

• Formation of stigma at the apex of the follicle

• Factors involved in rupture of the preovulatory follicle– Digestion of matrix proteins

by enzymes

• Process of ovulation– Similar to that of

inflammation• Production and

accumulation of PGs• Infiltration of immune

cells

Regulation of luteal function

• Luteal cells– Small (around 25 % of total cells in the CL)

• Very small contribution to basal production of progesterone

• Responds to LH and produce progesterone (5 to 20 X above the basal level)

– Large (around 10 % of total cells in the CL)• Very high

• No significant response to LH

• Hormonal factors– LH

• Extremely crucial during development• May not be necessary during the middle of luteal

phase

– Estradiol• Only in some species (i.e. rabbits)

– Prolactin• During early stage of pregnancy in rats and mice

Luteolysis

• Death of luteal structure– Formation of CA

• Active or passive– Active

• Uterine secretion of luteolytic agent – PGF2

– Passive• Loss of luteotropic agent

Active luteolysis

• Communication from uterus to ovary

– Production of PGF2

• Approximately 4 days before estrus

– PGF2diffuses into the bloodstream feeding the ovary bearing the CL (ovarian artery)

• Counter-current exchange PGF2

Uterinevein

Ovarian artery

Large black arrows indicatedirection of PGF2 flow

• From uterus to ovary – Interaction of PGF2

with its receptors on the CL

• Elevation of Ca release by the ER

• Decreased production of progesterone

• Ultimately death of the luteal cells

• Release of oxytocin.

PGF2

Progesterone

Oxytocin

PGF2

Changes in hormones during proestrus

• From ovary to uterus (and back to the ovary)– Oxytocin enters the

bloodstream and reaches the uterus and stimulates production of more PGF2.

– Increasing amount of estradiol from the large follicle enters bloodstream and also reaches uterus and causes increased production of PGF2 by uterus through increased sensitivity to oxytocin

PGF2

Progesterone

Oxytocin

PGF2

Changes in hormones during proestrus

• From ovary to uterus (and back to the ovary)– The relationship between

uterine production of PGF2 and production of oxytocin by the CL

• A positive feedback loop – Production of the first

hormone (i.e. PGF2) stimulates production of the second hormone (i.e. oxytocin), and increased production of the second hormone causes further production of the first etc.

PGF2

Progesterone

Oxytocin

PGF2

• Communication from uterus to ovary during pregnancy– As stated above, proestrus

begins when Progesterone production by CL begins to decline.

– This decline is initiated by increased production of PGF2Increased production of PGF2 is ablated when pregnancy has been initiated, resulting in continued Progesterone production by the CL and pregnancy maintenance.

PGF2

Progesterone

Pregnancy