1. Ovarian structures and function

2. Structures on the Ovaries and Their Function
Characterized as an organ of constant change
A series of dynamic changes in a very predictable manner during the reproductive cycle.

3. 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.

4. Destruction of the corpus luteum (CL)
Prostaglandin F2alpha (PGF2a) 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

5. 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

6. Sections of Ovaries Two distinct regions. Cortex Medulla
cortex (outer)
medulla (inner)
Cortex
Medulla

7. 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
Cortex
Medulla

8. Ovarian Cortex Follicles The CL
Eventually grow and become capable of undergoing ovulation
The CL
Cells/tissues responsible for production of estradiol and progesterone
Cortex
Medulla

9. Ovarian Medulla The ovarian medulla Cortex Medulla
The central area of the ovary
Made of dense connective tissues
Contains blood vessels, nerves, and lymph ducts.
Cortex
Medulla

10. 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

11. Follicles Secondary 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
Primary
Primodial
Preantral follicles
Secondary
Primary
Primodial

12. Follicles Antral follicles Antral follicles Antral follicles Antral
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

13. Follicles Basement membrane Granulosa cells Antrum Oocyte
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
Oocyte
Theca externa
Theca interna

14. 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

15. 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

16. 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

17. Luteal structures CH CH Early CH Developing CH
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 CH
Developing CH

18. Luteal structures The corpus luteum (yellow body) CL CL with cavity CL
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 with
cavity CL
CL without
cavity

19. 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

20. Pattern of follicular development and changes in blood hormone concentrations
Ovulation
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 E2
FSH

21. Pattern of follicular development and changes in blood hormone concentrations
Ovulation
Decrease in blood FSH
Partly caused by increased estradiol concentrations in the blood
Negative feedback.
Estradiol
FSH

22. Pattern of follicular development and changes in blood hormone concentrations
Ovulation
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
FSH

23. Pattern of follicular development and changes in blood hormone concentrations
Ovulation
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
Subordinate
Follicles
FSH
Deviation

24. Pattern of follicular development and changes in blood hormone concentrations+ LH
Ovulation
FSH
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.

25. Pattern of follicular development and changes in blood hormone concentrationsLH
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).
(-) + + + P4 CL

26. Pattern of follicular development and changes in blood hormone concentrations+ LH
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).

27. Pattern of follicular development and changes in blood hormone concentrations+ LH
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.

28. Pattern of follicular development and changes in blood hormone concentrations
Ovulation
Ovulation
Ovulation CH CL C
Adapted from
Lucy et al., 1992
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

29. Pattern of follicular development and changes in blood hormone concentrationsCL CH
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
Ovulation
Ovulation
Ovulation
Two Waves
Ovulation CH
Ovulation
Ovulation
Three Waves
Adapted from
Lucy et al., 1992

30. 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

31. 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

32. 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

33. 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

34. Hormonal factors LH Estradiol Prolactin
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

35. Luteolysis Death of luteal structure Active or passive Formation of CA
Uterine secretion of luteolytic agent
PGF2a
Passive
Loss of luteotropic agent

36. Active luteolysis Communication from uterus to ovary
Ovarian artery
Communication from uterus to ovary
Production of PGF2a
Approximately 4 days before estrus
PGF2a diffuses into the bloodstream feeding the ovary bearing the CL (ovarian artery)
Counter-current exchange
Uterine
vein
PGF2a
Large black arrows indicate
direction of PGF2a flow

37. From uterus to ovary Interaction of PGF2a with its receptors on the CL
Progesterone
From uterus to ovary
Interaction of PGF2a 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.
Oxytocin
PGF2a
PGF2a

38. Changes in hormones during proestrus
Progesterone
From ovary to uterus (and back to the ovary)
Oxytocin enters the bloodstream and reaches the uterus and stimulates production of more PGF2a.
Increasing amount of estradiol from the large follicle enters bloodstream and also reaches uterus and causes increased production of PGF2a by uterus through increased sensitivity to oxytocin
Oxytocin
PGF2a
PGF2a

39. Changes in hormones during proestrus
From ovary to uterus (and back to the ovary)
The relationship between uterine production of PGF2a and production of oxytocin by the CL
A positive feedback loop
Production of the first hormone (i.e. PGF2a) stimulates production of the second hormone (i.e. oxytocin), and increased production of the second hormone causes further production of the first etc.
Progesterone
Oxytocin
PGF2a
PGF2a

40. Communication from uterus to ovary during pregnancy
Progesterone
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 PGF2a. Increased production of PGF2a is ablated when pregnancy has been initiated, resulting in continued Progesterone production by the CL and pregnancy maintenance.
Pregnancy
PGF2a