14.3 - Reproductive Endocrinology Flashcards
Leydig Cells
- in the male testes
- produce testosterone
Sertoli Cells
- in male testes
- produce 2 hormones
1) Androgen-Binding Protein (ABP)
2) Inhibin
= resident cells of seminiferous (germinal) epithelium - FXN: to nurture, support, control spermatogenesis
- divide the epithelial space into basal and luminal compartments via tight JXNs with each other
–> contribute to the blood-testes barrier
Granulosa Cells
- in female ovary
- surrounding developing oocytes
- produce estrogen
- for short time after ovulation, with the theca cells, produce estrogen + progesterone
Theca Cells
= ovarian stromal cells
- produce estrogen and progesterone in conjunction with granulosa cells for a short period after ovulation
Placental Hormones
- estrogens
- progesterone
- chorionic gonadotropin (hCG)
Spermatogenesis
- Stem cell = type A dense spermatogonia
- mitotic divison produces: Type A dense, Type A pale, Type B pale spermatogonia
- 1st division of meiosis –> primary spermatocytes
- 2nd division of meiosis –> secondary spematocytes
Spermiogenesis
= after mitotic divisions, morphological differentiation of cells into final spermatocyte structure = spermatids (early and late)
Spermatozoa
- singular = spermatozoan
- after spermiation
- are the cells that are released into the lumen
Residual Bodies
= membrane bound bags of excess cytoplasm
- are shed at the end/after spermiation
- at the same time the cell’s (spermatid’s) connections with each other are broken
- accumulate in lumen of seminiferous epithelium
Oogonia
- only undergo mitosis during embryonic life
- remain trapped in a stage prior to 1st meiotic division for majority of life
Primary Oocyte
- oogonia in meiosis I
Secondary Oocyte
= ovulated cell
- the first meiotic division is completed just prior to ovulation
Ovum
- fertilization triggers further development
- -> cell is then called ovum
Zygote
= term for genetically novel cell created why the male and female pronuclei combine to restore a diploid nucleus
Follicular Developmental Stages in Ovary
1) Primordial Follicles
2) Primary follicle
3) Preantral Follicle
4) antral follicle
5a) atretic follicle
5b) Graafian follicle
Primordial Follicles
- -> consists mostly of oocyte surrounded by layer of squamous follicular cells and a basement membrane
- this is the stage in which oocytes exist for most of their lifetime
- exists from birth until start of follicular development at puberty
Primary follicles
- follicles which have attained a receptivity for FSH
- recognized by transformation of follicular cells to a cuboidal (or rounded) form = granulosa cells
- zona pellucida is secreted around the oocyte
Granulosa cells
= transformation of the follicular cells from a squamous to a cuboidal (or rounded) form
- occurs in primary follicles stage
Zona pellucida
= glycoprotein coat
- contains ZP-proteins –> important in sperm binding
- secreted around the oocyte in the primary follicle stage
Pre-antral follicle
- results from mitotic expansion of the granulosa cells
- granulosa cells secrete liquor folliculi which collects extracellularly –> eventually will form the antrum region
Antral Follicle
- once the liquor folliculi secreted from the granulosa cells has sufficiently collected extracellularly to segregate from the granulosa cells - it forms the antrum region
- these follicles are big enough and have a well-defined antrum
- granulosa cells surrounding the antrum are organized into 3 regions:
1) Mural cells
2) Corona radiata
3) Cumulus oophorus - development to this point takes 5-6 weeks
Mural Cells
= region of granulosa cells closest to the follicular basement membrane
Corona Radiata
= region fo granulosa cells surrounding the oocyte
Cumulus Oophors
= “cloud of the egg”
- region of granulosa cells bridging between the corona radiate and mural cells
Atretic follicles
= way that a majority of all follicles (regardless of stage) end their existence
- effectively undergoing a controlled death
Graafian follicle
= any follicle selected for ovulation during a monthly cycle –> transforms into a macroscopic size
Theca Intera Cells
= functionally specialized overaian stromal cells outside larger follicles
- sequester cholesterol for use by the granulosa cells in making estrogen
Theca externa cells
- adopta myofibroblast morphology
- aid the physical expulsion of the oocyte at ovulation
Ovulation
- corona radiata + liquor folliculi are expelled
- along with the secondary oocyte
After ovulation
- no longer have BM separating theca cells from granulosa cells
- -> both cells adopt different morphology corresponding to altered availability of enzymes and precursors to both cell types
- theca intern cells –> theca lutein cells
- granulosa cells –> granulosa luetin cells
Corpus Luteum
= “yellow body”
= steroid-secreting structure
- formed by theca lutein cells + granulosa lutein cells
- in the absence of pregnancy, (signaled by hCG) this structure resolves back to undifferentiated stromal tissue
Corpus Albicans
= scar formed by unresolved tissue
What is Spermatogenesis
= from spermatogonia to spermatozoa
- meiotic division followed by differentiation
- in humans is between 69-80 days for the total cycle
- at any given point the entire cycle is happening at the same time in seminiferous epithelium
- up to 5 generations may be represented
What is spermiogenesis
- morphologic differentiation (spermatid) through permeation
What are Spermatogonia, and the different types of them
= germ cells (2n)
- cells underling mitotic division
- oval cells next to BM
- three types of spermatogonia
1) type A dense = true stem cell
2) type A pale
3) type B pale - pale indicated more euchromatic nucleus, and will be fewer in number
What are Spermatocytes, and different types of them
- when cells are undergoing meiosis
- 2 types of spermatocytes (histologically indistinguishable without antibody staining)
1) primary spermatocytes = in meiosis 1 (2n) - very recognizable because chromosomal material is in stages of meiotic division
- cross from basal toward apical aspects of cells
- cells before completion of meiosis I
- located in basal (abluminal) compartment)
- labeled with mini = mrine gene involved in regulation of transcription
2) secondary spermatocytes = in meiosis 2 (n) (a very short lived stage - hard to find these cells) - before completion of meiosis II
- adluminal compartment
What are spermatids
= cells as they undergo morphological differentiation (n) –> change from round cell to mature sperm cells
- 1st change in nucleus
- develop flagella
- loose lot of cytoplasm in structure call residual body
- spermiogenesis is from here until spermiation (where the spermatids are released into lumen)
Type A dense spermatogonia
= true stem cell
- dense because nucleus is very heterochromatic
- oval cells
- right next to BM
- elongated cells in the direction of BM
Type A pale spermatogonia
- cells that are mitotically active
- pale indicates more euchromatin in nucleus
Tybe B pale spermatogonia
- cells in their final mitotic divisions
- are about to become spermatocytes
- pale indicates more euchromatin in nucleus
what are Sertoli Cells (include functions, important connections, morphology, freeze-fracture)
- resident cell - connect with each other via tight junctions
–> effectively creates basal + lumenal compartment in epithelium - 2 compartments separate self from non-self MHCs
- connect with developing germ cells via gap junctions = mechanism for regulating germ cell development
- morphology = highly euchromatic nucleus, ovoid, elongated along radial direction from epithelium (LM); see tight junctions (EM)
- freeze fracture:
E-face) shows sertoli-sertoli cell tight junctions
P-face) shows sertoli-germ cell gap junctions
What occurs In the Spermatid stage
- spermatid undergoes morphological changes = process called spermiogenesis
- spermiogenesis = process of morphological differentiation that occurs in spermatid phase
- begins with formation of acrosomal cap around nucleus
- acrosome cap forces neckless into oval then later into a pear shape as the acrosome is developed
- intracellualr organelles (mitochondria + microtubules (Manchette)) are developed
- flagella is developed and the residual body is shed
Manchette Microtubules
- function is to aid in squeezing spermatid cell down into shape expected of a mature spermatid
What are 4 phases of spermatogenesis and key features of each
1) Golgi Phase
- golgi, mitochondria, acrosomal vesicle, centriole
2) Cap Phase
- developing axonemal complex
- acrosomal cap forms –> forces nucleus into oval shape
3) Acrosome phase
- acrosome forces nucleus from oval to pear shape
- manchette microtubules begin to function
4) Maturation Phase
- flagellar tail is developed
- residual body is being shed
Regions of spermatid body
- head region - contains acrosomal cap. nucleus, manchette microtubules
- neck region - location where residual body is shed
- middle piece –> annulu –> principal piece (end tail)
2 types of spermatids
1) Early spermatid
- round to oval nuclei
2) Late spematid
- pointed nuclei
- long flagellar tail
describe the Germ cell connections in males
- developing cells remain physically connected to each other until loss of residual bodies
- functions to maintain waves of developing germ cells (why they all appear in similar stages)
- germ cells are connected via gap junctions with sertoli cells
What is spermiation
= final stage of spermiogeneiss
= process of release of spermatid by sertoli cell
- spermatozoon (spermatozoa) = cells that are free in lumen
= “sperm”
why did he mention orchitis in the video?
- from mumps
- sertoli cells keeps immune system cells present in infection response from entering apical compartment
- -> kept in basal compartment to prevent immune reaction with sperm
Describe the final stage of sperm development
- sperm acquire a glycoprotein coat in epididymis
- -> important for passing through female reproductive tract
- capacitation occurs later = process where this coat is later removed by contact with cilia in female reproductive tract –> necessary for sperm adhesion to occur
Describe the full maturation of sperm WRT to capacitation and motility
- full motility is conferred by prostatic fluid at ejaculation
- fructose from seminal vesicles provides energy for motility
- capacitation - occurs in female genital tract
= removal of glycoprotein coat acquired in epididymis - allows spermatozoa (which can survive in female tract for up to 5 days) to bind sperm receptors in zone pellucida
Unilaminar primary follicle
= beginning of follicular development
- under hormonal control
- occurs after puberty
- oocyte enlarges and matures
- characterized by change of follicular cells squamous to cuboidal shape –> called granulosa cells
Multilaminar primary follicle
= granulosa cells start to divide and are present in multiple layers
- stromal cells form theca follicle
- oocyte secretes zona pellucida (dark eosinophilic structure)
- oocyte + granulosa cells remain connected via gap junctions
- BM excludes blood vessels, Mural granulosa cells = cells next to BM
Early secondary follicle
= defined by presence of fluid filled space among granulosa cells = antrum - filled with liquor folliculi
- theca folliculi comprised of
1) theca interna - steroidogenic
- secrete estrogen precursors
2) theca extern - contains fibroblast + smooth muscle
- granulosa cells –> convert the estrogen precursors to estrogens
- secondary follicles form the follicular pool
Selectable pool
- in a ny month there is a selectable pool of follicles = cell that are responsive to gonadotropins (20-30 at any given time)
- once per month a selected follicle will be the follicle that is chosen to become graafian follicle (is the most fully responsive to gonadotropins)
Late secondary/graafian follicle
- novel expression of LH receptors on theca intern cells + FSH receptors on granulosa cells
- -> allow secondary follicle to be “selected” for ovulation
- selected follicle grows v. large over the course of one follicular phase (1mm–>2cm), 10 days prior to ovulation
- 3 divisions of granulosa cells are present
1) Mural granulosa cells
2) Cumulus oophorus
3) Corona Radiata
Describe the 3 divisions of granulosa cells
1) Mural granulosa cells
- against the BM
2) Cumulus Oophrous
- pad (“cloud”) of granulosa cells
- where oocyte rests + is suspended in antrum
3) Corona radiata
- granulosa cells directly surrounding the oocyte
- at ovulation these cells are expelled with oocyte and go with it down the female reproductive tract
Morphology of the stromal cells of follicle
1) Theca interna
- puffy cholesterol containing cells
2) Theca externa
- myeloid looking cells
- layer is in part responsible for squeezing out oocyte at time of ovulation
Describe how steroidogenesis is critically affected by presence of follicular BM and the changes that occur when it is broken down
- Theca intern cells produce a steroid precursor from cholesterol –> pass to the granulosa cells across the BM
- the precursor = androstenedione –> it can cross BM and get to granulosa cell to be made into estrogen
- circulating estrogen levels correlate with # of granulosa cells present
- after ovulation - no longer have the BM
- -> theca lutein + granulosa lutein cells collaborate to produce both the steroid hormones present in that phase (estrogen + progesterone)
- -> theca intern cells go from puffy to normal = theca lutein cells
- -> granulosa cells go from normal to puffy = granulosa lutein cells
What are the corresponding “Safe” terms for the stages of follicle maturation
- unilaminar Primary follicle = primary follicle
- multilaminar primary follicle = pre-antral follicle
- secondary follicle = antral follicle
- Graafian (tertiary) follicle = Graafian follicle
