Female Reproductive System Flashcards
What covers the ovaries?
- A dense CT capsule, the tunica albuginea
2. A layer of mesothelium (cuboidal / squamous) on the outside
What are the two parts of the ovary and what is found in them?
- Outer cortex - portion beneath tunica albuginea. Consists of ovarian follicles + stroma
- Medulla - central core, consists of loose connective tissue, blood vessels, lymph vessels, and nerves
No distinct boundary
What is the ovarian stroma?
Connective tissue containing collagen fibers, ground substance, smooth muscle cells, and fibroblast like cells which is found in the outer cortex
What type of oocyte do primordial follicles have?
One oocyte arrested in prophase 1 of Meiosis 1 (diplotene stage). Called primary oocyte. They can stay in this phase for 12-50 years.
What type of cells surround the oocyte in primordial follicles? What surrounds them?
A single layer of squamous cells called follicular cells. They are surrounded by a basal lamina, which is surrounded by the connective tissue of the ovarian cortex.
What are the two types of primary follicles?
- Unilaminar primary follicle - early stage, 1 layer of granulosa cells
- Multilaminar primary follicle - later stage, 3-5 layers of granulosa cells
What changes occur from primordial to primary follicle?
- Squamous follicular cells become cuboidal granulosa cells, which can have multiple layers
- Primary oocyte secretes zona pellucida, between it and the granulosa cells
- Cortical granules appear in the ooplasm of the primary oocyte via TEM
- Gap junctions are made between microvilli of oocyte and granulosa cells, and also between neighboring granulosa cells. This is for transfer of metabolites.
- Theca begins to form.
What is the Zona Pellucida and how does it stain?
The layer forming in the primary follicular stage consisting of four major glycoproteins ZP1-4, secreted by the primary oocyte. It is between granulosa cells and oocyte.
Stains pink / red with H&E, and magenta with PAS (glycoprotein)
What are cortical granules for?
They contain proteases that are released if the oocyte is fertilized by sperm. Cortical reaction is used to block multiple fertilization events
What are theca cells, their two types, and when do they form?
They are connective tissue cells surrounding the basal lamina of the granulosa cells.
Theca interna: well vascularized with endocrine characteristics
Theca externa: less well vascularized, blends in with CT stroma of ovarian cortex
They form in the primary follicular stage but are best seen in secondary follicular
What changes occur from primary follicle to secondary (antral) follicle?
- Primary follicle moves deeper into cortex due to increase in size from proliferation of granulosa cells.
- Antrum appears among granulosa cells.
- Theca layers become well defined.
- Cumulus oophorus / cumulus mass forms
- Oocyte stops increasing in size.
- Corona radiata forms
- Estrogen stimulates granulosa proliferation, increasing follicular size
What factors stimulate the growth of the primary follicle?
FSH, growth factors, and calcium
What stops the oocyte from increasing in size during the antral stage?
oocyte maturation inhibitor (OMI) that is secrete by the granulosa cells into the antral fluid
What forms the cumulus mass?
When a mound of granulosa cells becomes eccentrically located in the secondary / antral follicle
What is the corona radiata?
Granulosa cells of the cumulus mass that immediately surround the oocyte and remain with it during ovulation
What fluid fills the antrum?
Liquor folliculi - composed mainly of hyaluronic acid, as well as other hormones and growth factors such as oocyte maturation inhibitor
What is the function and stimulation of the theca interna cells?
Steroid-secreting endocrine cells which have receptors for luteinizing hormone (LH). They synthesize and secrete androgens + some progesterone, which pass through the basal lamina and are uptaken by granulosa cells
What do granulosa cells do under FSH control?
Convert the androgen androstenedione from theca interna cells into estradiol. Estrogen stimulates granulosa cell proliferation, increasing the size of the follicle.
During what stage do granulosa cells start to get LH receptors?
Secondary / antral stage
What characterizes the Graafian follicle stage?
- Large antrum, zona pellucida, and detachment of oocte and corona radiata from rest of cumulus oophorus.
- Completion of Meiosis I up until Metaphase II prior to ovulation due to LH surge.
What is released during ovulation?
Secondary oocyte, granulosa cells of corona radiata, and granulosa cells of the cumulus mass.
What happens to the lumen of the corpus luteum, which was occupied by the antrum of the follicle?
It is replaced by a blood clot and then by connective tissue.
What do the theca interna and granulosa cells become in the corpus luteum? How do they appear?
Theca interna: Theca lutein cells - small, less cytoplasm, basophilic
Granulosa: Granulosa lutein cells - large, eosinophilic
The theca cells invade into the granulosa and appear as strands.
What is meant by “luteinization”?
Luteinization = cells become filled with lipid, induced by LH surge. This works because both granulosa cells and theca interna cells now possess LH receptors. Both cell types will now produce mainly progesterone and some estrogen.
What is the corpus albicans?
If pregnancy does not happen, and the corpus luteum is not maintenanced by hCG, the luteinized cells become and irregular, highly folded, glassy, eosinophilic structure called corpus albicans.
Most of the cells left are macrophages.
What are atretic follicles?
Primordial follicles which start development as primary follicles, but do not develop into mature ova (only 400 mature ova out of 600,000-800,000 primordial at birth.). They degenerate via atresia.
What happens to form atretic follicles?
- Apoptosis of granulosa cells.
- Granulosa cell layer invaded by neutrophils and macrophages.
- Granulosa cells slough into antrum
- Theca interna hypertrophy
- Follicle collapses as degeneration continues.
- Connective tissue invades into follicle cavity.
What types of atretic follicles can be seen and how are they distinguished from the corpus albicans?
Only ones larger than primary follicles.
- Zona pellucida will be recognizable as an eosinophilic band.
- Corpus albicans is much larger and thicker, with no ZP
- Basal lamina thickens, folds, and becomes eosinophilic as a “glassy membrane” in atretic follicles.
What are the four regions of the uterine tube and what characterizes them?
- Infundibulum - funnel-shaped with fimbriae, which move close to surface of ovary at time of ovulation for uptake of oocyte.
- Ampulla - longest segment, where fertilization takes place
- Isthmus - narrow region near uterine wall
- Intramural (uterine part) - opens into cavity of uterus
What cells characterize the mucosa of the uterine tube?
Simple columnar epithelium
- Ciliated columnar - for motion of the oocyte
- Non-ciliated columnar - Peg cells - secrete fluid containing nutrients for spermatozoa and ova
What is the hormonal control of the mucosa of the uterine tube?
Estrogen controls hypertrophy during follicular phase and atrophy during luteal phase of uterine cycle - the epithelium is highest at time of ovulation. This stimulates ciliogenesis in ciliated columnar cells.
Progesterone increases the number of secretory / peg cells
What is the muscularis layer of the uterine tube and what is its function?
Inner circular, outer longitudinal. Peristaltic contractions + beating of cilia towards the uterus help move the ovum towards the uterus
What glands are found in the oviduct? Is it serosa or adventitia?
No glands - just the peg cells. It is covered by a serosa, since it has a peritoneal covering?
What sections of uterine tube have more / less mucosal folds?
Ampulla has most folds of mucosa projecting in the lumen of the oviduct. The isthmus + intramural segments have less.
What are the three parts of the uterus?
- Body - expanded upper region of uterus
- Fundus - rounded part where oviducts join - similar to body histologically
- Cervix - lower part protruding into upper vagina
What are the three layers of the wall of the body + fundus of the uterus?
- Endometrium - Mucosa
- Myometrium - Muscularis
- Perimetrium - outer layer, serosa
How is the smooth muscle of the myometrium organized? What happens to it during pregnancy or menopause?
Three layers of smooth muscle in indistinct layers. Pregnancy - hypertrophy + hyperplasia
Menopause - atrophies in the absence of estrogen
What is the stratum vasculare? What arteries does it include?
The larger blood vessels of the uterus, found mostly in the myometrium. Includes uterine artery and its branch, the arcuate arteries which course circumferentially within the myometrium
What type of epithelium is the endometrium and what cells are contained?
Simple columnar epithelium - ciliated cells and secretory cells. This also lines the uterine glands
What type of glands are uterine glands and how deeply can they extend? What surrounds them?
They are simple tubular or simple branched tubular, and may reach all the way to the myometrium.
They are surrounded by a collagenous connective tissue called the stroma
What are the two layers of the endometrium?
- Functional layer - lost during menstruation, many structural changes occur
- Basal layer - not lost during menstruation, few structural changes occur, regenerates functional layer
What is the blood supply to the endometrium?
Basal layer - supplied by straight arteries branching off of arcuate arteries from stratum vasculare of myometrium
Functional layer - supplied by spiral / helical arteries which give off arterioles supplying capillary beds. These branch from arcuate arteries.
How does the blood supply to the endometrium change during the uterine cycle?
Spiral arteries in the function layer degenerate with each uterine cycle during the menstrual / ischemic phase, caused by periodic contraction of the walls of the spiral artery segments
Straight arteries in the basal layer remain unchanged
What are the three phases of the uterine cycle and what hormones drive them?
- Proliferative (follicular) phase - Estrogen
- Secretory (Luteal) phase - estrogen + mainly progesterone, as in corpus luteum
- Menstrual (ischemic) phase - none
What happens during the proliferative / follicular phase?
Growth + maturation of ovarian follicles + secretion of estrogen causes mitosis of basal layer of endometrium, and the functional layer is rebuilt. The epithelial cells in basal layer reconstitute the uterine glands to resurface the endometrium. Spiral arteries extend to upper 2/3 of endometrium.
What happens to the uterine glands during the the secretory / luteal phase and why?
They enlarge and take on a corkscrew shape because they become filled with glycogen and glycoproteins produced by secretory cells.
How does the follicular phase endometrium appear histologically?
Uterine glands appear straight and with a narrow lumen
What happens to the endometrial stroma during the luteal phase? They differentiate into something!
Stroma becomes edematous, and enlarge due to accumulation of glycogen. The estrogen + progesterone allow them to differentiate into decidual cells which would let them form decidua basalis if implantation occurred?
How do the spiral arteries change from follicular to luteal phase?
Follicular - extend to upper 2/3
Spiral - become more coiled and extend nearly to the uterine surface
What happens during the menstrual / ischemic phase?
Epithelial cells of uterine glands stop secreting glycogen, the stroma loses fluid, and the stromal cells become more densely packed. Interruptions of blood flow result in sloughing of stromal and epithelial cells, blood, and uterine fluid -> menstruation
What is endometriosis?
Presence of endometrial tissue in pelvis or peritoneal cavity. This can undergo cyclic changes outside the uterus, and cause hemorrhage, adhesions and pain, forming a fibrotic mass and causing sterility.
What is the endocervix and what epithelium lines it?
The canal running between the uterine and vaginal cavities.
Epithelium - simple columnar with many mucus secreting cells and some ciliated cells
Where are cervical glands and what influences them hormonally?
They are deep branched invaginations of the surface epithelium of the endocervix. They do not undergo any histological changes during the uterine cycle, but estrogen regulates their glandular secretions
How does estrogen influence cervical glands?
Estrogen is highest prior to ovulation -
High estrogen = gland mucus is thinner and has alkaline pH - good for sperm
Lower estrogen = gland mucus is thicker and has an acidic pH - harmful to sperm
What is it called when ducts of cervical glands become occluded with secretions?
Nabothian cysts
What is the exocervix and what happens at the junction of endocervix and exocervix?
The external surface that protrudes into the vagina. Endocervix epithelium is simple columnar, and changes abruptly to stratified squamous non-keratinized for exocervix.
What is the purpose of the pap smear?
Cervical cancer starts at carcinoma “in situ” which is not metastatic but may metastasize later, and pretty much always begins with the stratified squamous non-keratizined epithelium of the exocervix.
What defines the mucosa of the vagina? How does it change with uterine cycle?
Stratified squamous non-keratinized with underlying lamina propria. The epithelium stores glycogen under influence of estrogen, and the most glycogen is stored at time of ovulation (cells may appear large and clear).
How can you differentiate vagina from esophagus?
There are no submucosal glands or muscularis mucosae in the vagina.
What defines the muscularis layer and outer layer of the vagina?
Muscularis - illdefined circular bundles of smooth muscle + a well defined longitudinal layer
Outer layer - adventitia of collagenous tissue containing elastic fibers, large blood vessels, and nerves
What type of glands are mammary glands?
Compound tubuloalveolar, modified apocrine sweat glands -> only true apocrine gland in the body.
How are lobes and lobules of the mammary gland defined and what do they drain into?
Lobules - have intralobular connective tissue between them which is loose connective tissue
Lobes - have interlobular connective tissue between lobes, which is dense irregular
Drain into: surface of nipple via a lactiferous sinus and duct
What forms the ducts of the mammary gland?
Simple cuboidal epithelium, with myoepithelial cells between epithelium and basal lamina
What changes inactive mammary gland undergo during the uterine cycle?
Some proliferation of ducts + transient edema due to estrogen stimulation, but largely unchanged.
What are the roles estrogen and progesterone in the proliferating / pregnant mammary gland?
Estrogen - stimulates proliferation of epithelium of intralobular ducts into milk-secreting cells
Progesterone - stimulates growth of secretory alveoli
Both factors cause breast enlargement. The ducts and secretory alveoli are lined by simple cuboidal epithelium
How does the connective tissue change during the proliferating phase of the mammary gland?
Adipose + connective tissue decreases due to growth of secretory acini. Plasma cells, lymphocytes, and eosinophils infiltrate
What is the major histological difference between proliferating and lactating mammary gland?
Lumens of secretory alveoli dilate due to accumulation of milk
How are the milk protein-containing secretory vesicles in secretory cells released?
Merocrine secretion
How is the lipid component of milk released?
Apocrine secretion
What is colostrum and how is it unique?
It is the milk produced for first 2-3 days after childbirth. It contains more protein and few lipids than regular milk, and secretory IgA and IgG produced by plasma cells is found in it to give newborns passive immunity.
What is the function of prolactin and what is its role in changing milk composition?
During pregnancy, estrogen and progesterone suppress release of prolactin.
Prolactin stimulates production of lipid-rich milk. After pregnancy, when estrogen and progesterone levels drop, it is released to change the colostrum to regular lipid-rich milk
What is the reflex for milk ejection?
Suckling -> neural sensory reflex to release milk. Supraoptic and paraventricular nuclei target neurohypophysis, which releases oxytocin which stimualtes myoepithelial cell contraction of alveoli + ducts leading to ejection of milk
What are the two types of breast cancer?
- Ductal carcinoma - cancer of ductal cells, which are caused to proliferate by estrogen every uterine cycle. Most common
- Lobular carcinoma - cancer of secretory alveoli. Less common