2Structures on the Ovaries and Their Function Characterized as an organ of constant changeA series of dynamic changes in a very predictable manner during the reproductive cycle.
3Cyclic changesDevelopment of large fluid-filled structures called folliclesRupture of the ovulatory follicle and release of the oocyte (ovulation)Formation of a corpus luteum from remnants of the ovulated follicle.
4Destruction of the corpus luteum (CL) Prostaglandin F2alpha (PGF2a) near the end of the cycle if pregnancy is not initiatedDemise of the CLDevelopment of an ovulatory follicle and release of the oocyte at ovulationSeries of events takes place in the predictable mannerOnce every three weeks in cowsOnce every four weeks in humans
5Association 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
6Sections of Ovaries Two distinct regions. Cortex Medulla cortex (outer)medulla (inner)CortexMedulla
7Ovarian Cortex The ovarian cortex The outer region of the ovary. Covered by a layer of connective tissue called the tunica albugineaNo ability to produce estradiol or progesteroneDoes not contain oocytesCortexMedulla
8Ovarian Cortex Follicles The CL Eventually grow and become capable of undergoing ovulationThe CLCells/tissues responsible for production of estradiol and progesteroneCortexMedulla
9Ovarian Medulla The ovarian medulla Cortex Medulla The central area of the ovaryMade of dense connective tissuesContains blood vessels, nerves, and lymph ducts.CortexMedulla
10Structures within the ovarian cortex FolliclesFive (5) different types present in the ovarian cortex at any given period of time during the reproductive cyclePrimordialPrimarySecondaryTertiaryAntral
11Follicles Secondary Primordial, primary, and secondary follicles Often referred to as preantral folliclesMicroscopic in sizeClassified individually (primordial versus primary versus secondary) based upon cell shape (flat vs. cube) and number of cell layers (one vs. multiple) surrounding the oocytePrimaryPrimodialPreantral folliclesSecondaryPrimaryPrimodial
12Follicles Antral follicles Antral follicles Antral follicles Antral have a hollow fluid-filled cavityAn antrum.Less pronounced in developing tertiary follicles.The fluid within the antrumFollicular fluidSize of antral follicles varies depending on the stage of follicular developmentSome antral follicles (> 1 mm) are visible on the surface of the ovary as blister-like structuresAntralfolliclesAntralfollicles
13Follicles Basement membrane Granulosa cells Antrum Oocyte The wall of a follicleComposed of three distinct cell layersThe inner most layer (facing the antrum)Granulosa cellsThe second layer of cellsTheca internaThe outer most layer (facing ovarian cortex)theca externaTheca interna and theca externaTheca cellsGranulosa cell layer is separated from theca cell layer by a thin membrane called a basement membrane.AntrumOocyteTheca externaTheca interna
14FolliclesBoth theca and granulosa cells are involved in production of estradiolTheca cells produce androgensGranulosa cells convert androgens to estradiolGranulosa cellsNurse cells by producingNumerous materials essential for development of the oocyte
15Luteal structures After ovulation The oocyte is released from the preovulatory follicleTheca and granulosa cells remaining in the follicular wall undergo dramatic changesFormation of a corpus luteum.A shift from producing estradiol (granulosa) and androgen (theca) to producing large amounts of progesterone
16Luteal 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
17Luteal structures CH CH Early CH Developing CH The corpus hemorrhagicum (bloody body)During the early part of the luteal phase of the reproductive cycleAppears redSmall blood vessels within the follicle rupture during ovulationCollapse of follicular wall into many folds after leakage of follicular fluid into many foldsCHCHEarly CHDeveloping CH
18Luteal structures The corpus luteum (yellow body) CL CL with cavity CL Found during the middle part of the luteal phase of the reproductive cycleThe major source of progesteroneSome have a CL with a very large fluid-filled cavity, whereas others have a CL without a distinguishable cavityCLCL withcavityCLCL withoutcavity
19Luteal structures The corpus albicans (white body) A white, fibrous tissueRemains of the CLLoss of ability to produce progesteroneDeath of cells in the CLIt eventually completely loses the ability to produce progesteroneLeads to follicular phaseCACAEarlyCAAdvancedCA
20Pattern of follicular development and changes in blood hormone concentrations OvulationSecondary FSH surgeImmediately after ovulationA group of small (3 to 4 mm in diameter) antral follicles (cohort) begins to grow as FSH concentrations peakEmergenceFollicles continue to grow in size and produce estradiol as blood concentrations of FSH begin to declineE2FSH
21Pattern of follicular development and changes in blood hormone concentrations OvulationDecrease in blood FSHPartly caused by increased estradiol concentrations in the bloodNegative feedback.EstradiolFSH
22Pattern of follicular development and changes in blood hormone concentrations OvulationDecline in blood FSH concentrationsSome of the follicles within a cohort stop growing and begin to die at this stageAtresiaA few follicles within the cohort continue to grow as FSH concentrations approach baselineGrowth rate slows down rapidly for all but one of these folliclesFSH
23Pattern of follicular development and changes in blood hormone concentrations OvulationThe follicle that is bigger than the rest of group when FSH concentrations reach baselineThe dominant follicleThe rest of follicles within the cohortSubordinate folliclesThe time point, in which the dominant follicle begins to grow faster than subordinate folliclesDeviation.Dominant FollicleSubordinateFolliclesFSHDeviation
24Pattern of follicular development and changes in blood hormone concentrations +LHOvulationFSHThe dominant folliclecontinues to grow even though blood concentrations of FSH are lowSubordinate follicles stop growing and undergo atresiaGrowth of the dominant follicle under low blood FSHAchieved by acquisition of LH receptors on the granulosa cells and a shift to LH responsivenessProduces a large amount of estradiol, and blood concentrations of estradiol increase.
25Pattern of follicular development and changes in blood hormone concentrations LHIncrease in blood estradiolNo preovulatory LH surge and ovulationThe newly formed CLProducing progesterone as it begins to grow at the same timeProgesterone inhibits preovulatory surges of GnRH and LH (this is also negative feedback).(-)+++P4CL
26Pattern of follicular development and changes in blood hormone concentrations +LHThe dominant follicleEventually reaches a size similar to that of the preovulatory follicle (growth plateau)Stops growing but actively produces estradiolLack of hormonal supportThe dominant follicle eventually stops producing estradiol and begins to undergo atresia (loss of dominance).
27Pattern of follicular development and changes in blood hormone concentrations +LHDecreased estradiol production by the dominant follicleRemoval of the negative feedback on FSHBlood FSH concentrations begin to increaseA new cohort of antral follicles begin to grow in the ovaryThe whole process, therefore, is repeated.
28Pattern of follicular development and changes in blood hormone concentrations OvulationOvulationOvulationCHCLCAdapted fromLucy et al., 1992The pattern of follicular development in human and cattle resembles that of a wave (follicular wave)One cohort of follicles emerges in the beginningOne of the follicles within the cohort becomes the dominant follicle and continues to growAfter reaching its growth plateau, the dominant follicle begins to shrink, and a new cohort emerges shortly thereafter
29Pattern of follicular development and changes in blood hormone concentrations CLCHDuring the reproductive cycle, females may develop two or three follicular waves, with the dominant follicle that develops during the last wave being the ovulatory follicleOvulationOvulationOvulationTwo WavesOvulationCHOvulationOvulationThree WavesAdapted fromLucy et al., 1992
30OvulationThe process by which the ovarian follicle physically rupturesRelease of the oocyteTransformation of follicular cells (theca and granulosa cells) into luteal cells
31Factors involved in rupture of the preovulatory follicle Build-up of the fluid pressure within the follicleThinning of the cell layersFormation of stigma at the apex of the follicle
32Factors involved in rupture of the preovulatory follicle Digestion of matrix proteins by enzymesProcess of ovulationSimilar to that of inflammationProduction and accumulation of PGsInfiltration of immune cells
33Regulation of luteal function Luteal cellsSmall (around 25 % of total cells in the CL)Very small contribution to basal production of progesteroneResponds to LH and produce progesterone (5 to 20 X above the basal level)Large (around 10 % of total cells in the CL)Very highNo significant response to LH
34Hormonal factors LH Estradiol Prolactin Extremely crucial during developmentMay not be necessary during the middle of luteal phaseEstradiolOnly in some species (i.e. rabbits)ProlactinDuring early stage of pregnancy in rats and mice
35Luteolysis Death of luteal structure Active or passive Formation of CA Uterine secretion of luteolytic agentPGF2aPassiveLoss of luteotropic agent
36Active luteolysis Communication from uterus to ovary Ovarian arteryCommunication from uterus to ovaryProduction of PGF2aApproximately 4 days before estrusPGF2a diffuses into the bloodstream feeding the ovary bearing the CL (ovarian artery)Counter-current exchangeUterineveinPGF2aLarge black arrows indicatedirection of PGF2a flow
37From uterus to ovary Interaction of PGF2a with its receptors on the CL ProgesteroneFrom uterus to ovaryInteraction of PGF2a with its receptors on the CLElevation of Ca release by the ERDecreased production of progesteroneUltimately death of the luteal cellsRelease of oxytocin.OxytocinPGF2aPGF2a
38Changes in hormones during proestrus ProgesteroneFrom 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 oxytocinOxytocinPGF2aPGF2a
39Changes 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 CLA positive feedback loopProduction 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.ProgesteroneOxytocinPGF2aPGF2a
40Communication from uterus to ovary during pregnancy ProgesteroneCommunication from uterus to ovary during pregnancyAs 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.PregnancyPGF2a