Female Reproductive Histology Flashcards
Ovary physiological information
Develop retroperitoneal and. Migrate into he abdominal cavity to become intraperitoneal
Contains a ovarian suspension ligament that contains all the neuro vasculature for the ovary
Is attached to the uterine body via the ovarian ligament also
Contains a surface epithelium that is simple cuboidal
Tissue layers (external -> internal)
1) tunica albuginea = external capsule composed of dense irregular CT similar to the tests except doesn’t form a septa
2) cortex = underlies the tunica albuginea and is mesoderm-derived. Supports the ovarian follicles and helps them undergo differentiation
3) medulla = intermediate mesoderm CT that supports ovarian neuro vasculature
Two cel types in ovarian follicles
1) oogenic cell lineage: lineage of cells derived from primordial germ cells that make the egg
2) follicular cells: mesoderm derived epithelial cells that surround the oogenic cell. Play a role in creating the blood-follicle barrier to protect the oocyte from maternal immune system
Early development of follicles
During week 4, primordial germ cells migrate into he gonadal primordia as long as the SRY gene is absent
- here they undergo severely rounds of mitotic divison to form millions of primary oocytes (which arise in prophase 1 until puberty)
- crossing over occurs before prophase 1 so all of the crossing over occurs before puberty
Primordial follicles
Are primary oocytes that are surrounded by flattened follicular cells (simple squamous)
- stay in the ovarian cortex until the ovarian cycle begins
Follicular atresia
Process in which follicular cells and oocytes of the follicle undergo apoptosis and are removed by phagocytic cells
- this seems counterintuitive to just make a million follicles and then kill over half of them off but there are two advantages
two advantages with this:
1) amount of estrogen produced is high if the number of primary follicles are high (this helps mature primary follicles when ovulating)
2) selectively protects against chromosomal abnormalities (although some still obviously get though) if there was no selective atresia, then there would be a very strong chance of chromosome abnormalities ring present (roughly 50%)
Primary follicles
At the start of each ovarian cycle, a small pool of primordial follicles (20ish) are activated by FSH and begin hyperplasia
- they migrate deeper into he cortex as well and severe allergies of these exhibit atresia at this time
Contains the primary oocyte which grows in size and nucleus enlarges. Also begins to create more rER and golgi complexes as well as cortical granules containing proteases
Cells surrounding in the primary follicular change to cuboidal from squamous and are now called granulosa cells
- these secrete inhibin which inhibits FSH synthesis and secretion
At this time the zona pellucida generates around the oocyte which allows for accurate fertilization. Has ZP3 and ZP4 proteins on surface which bind spermatozoa and induce the acrosomal response
Follicular theca cells also generate and differentiate into two different layers
Two layers of theca cells in the primary follicle
1) theca externa = outer fibrous layer composed of fibroblasts and smooth muscle fibers
2) theca interna = inner well-vascularized endocrine tissue that secretes androstenedione. The androstenedione paracrine signals to the granulosa cells which then convert it into estradiol (potent estrogen)
- the estradiol secretes back into theca cells and then is transported into the blood stream to both promote growth and inhbit GnRH and FSH/LH at there respective sites
Secondary antral follicle
As surviving primary follicles move deeper into he cortex (while still undergoing selective atresia), small cavities called antra form in the granulosa layer
- these secrete follicular fluid and eventually coalescence together into one large antrum
As the secondary follicle grows, forms three distinct regions
1) granulosa = steadied cuboidal layer that lines follicles
2) cumulus oophorus = loose collection of granuloma cells that forms a small hillock extending from granulosa layer
3) cornea radiata = tight collection of granulosa cells that surround the zona pellucida layer and will travel with the oocyte from the follicle
Ovulation
Occurs due to a massive surge of LH (and a smaller surge of FSH due to inhibin presence)
The oocyte with surrounding Zona pellucidum and cornea radiata layers is released from the ovary and follicle into the oviduct
The surge in LH also induces the following actions:
- primary oocyte completes meiosis 1 and gives rise to secondary oocyte and 1st polar body. The secondary oocyte arrests in metaphase 2 until fertilization occurs
- increases follicular fluid secretion by granulosa cells (contains prostaglandins, proteases, etc)
- impinged capillaries rupture and plasminogen degrades the collagen of the tunica albuginea
- smooth muscle fibers of theca externa contract in response to prostaglandins
- ovarian wall and follicle rupture release it everything from the follicle
Mature (Graafian) follicle
Follicle swells and matures as it gets closer to the medulla of the ovary
- forms a “stigma” which is where it starting to breach the surface of the medulla (this can be seen on ultrasound)
Usually only 1 follicle reach this stage (but if multiple do = more than one baby if fertilization occurs)
The follicle secretes a large amount fo estradiol and stimulates the hypothalamus and adenohypophysis to induce a LH surge
Corpus luteum
A transient endocrine gland that is formed as a result of ruptured follicle granulosa and theca cells undergoing changes in response to LH
always shows a blood clot within itself which is granules and theca cells collapsing on themselves
New cells that form
- theca lutein cells = formed from past thecal cells. secrete large amounts of progesterone and androstenedione.
- granulosa lutein cells = formed from past granulosa clels. Secrete inhibin and convert androstenedione into estradiol
- *progesterone and estrogen both inhbit FSH/LH in this stage while inhbin inhibts even further FSH
- the estrogen and progesterone work to prepare uterus for implantation and prevent further follicle movement/maturation. If pregnancy occurs, this doesnt decay fully and prevents menstration**
Without pregnancy occurring, the loss of LH causes the corpus luteum to cease production eventually and undergo apoptosis and phagocytosis
- this will induce the menstrual cycle and promote the next ovarian cycle (since there is no progesterone and both estrogen/inhbin respectively)
Uterus layers
Parametrium = outer layer of CT that is continuous with various uterine ligaments
- msot is serosa layer covered by mesothelium
Myometrium = middle thick highly vascularized layer. During pregnancy these smooth muscles undergo hyperplasia and hypertrophy to both support the fetus development and to prime for contractions once labor occurs
- the contractions are facilitated by the relapse of oxytocin (positive feedback)
Endometrium = inner layer with two distinct zones
1) functional layer = lumen layer lined with simple columnar epithelium and cillia as wellas underlying Lamina propria
- undergoes the most change during uterine cycle and also is the part that sloughs off during menstral cycle. Also contains the uterine glands
2) basal layer = inner layer that is highly cellular and contains most of the neuro vasculature (not all though)
- doesnt undergo much change and is not sloughed off during menstral cycle
Arterial blood supply of the uterus
Come from arcuate arteries found in the myometrium
- gives off two subsets of vessels
1) straight = provide blood supply to the basal layer of the endometrium
2) spiral arteries = supply the functional layer with blood
3 phases of the menstrual cycle
are controlled by LH and FSH levels and 1st day of menstrual phase is usually the first day of bleeding occurs (usually day 23 of the ovarian cycle)
1) proliferative phase
- takes place in conjunction with day 6-14of the follicle cycle and begins with primary -> secondary follicle
- is due to increased estradiol production which promotes regenerative growth of the functional layer
- uterine glands are straight with empty lumens and spiral arteries begin to elongate and induce angiogenesis as the functional layer hypertrophies
2) secretory (luteal phase)
- takes place with day 14-23 of the follicle cycle (right when ovulation occurs)
- is due to increased progesterone production
- uterine glands begin to fill with glycogen and dilate/coil up
- if fertilization occurs = stops here and doesn’t enter stage 3
3) menstrual phase
- takes place with day 23-28 if the oocyte is not fertilized
- is due to dropping of progesterone and estrogen levels
- blood supply to functional layer atrophied and casues leukocytes to invade tissues and degrade the basementmembrane separating the functional and basal layers
- the functional layer sloughs off and is expelled
Cervix
Inferior portion of uterus that contains simple columnar epithelium with a thick lamina propria
- lacks spiral arteries, does not undergo hyperplasia and does not slough off int he uterine cycle
Around the external os of the cervix = starts to transition to non-keratinized stratified squamous epithelium that is continuous with vaginal epithelium (this is the most common site of cervical cancer)
Under the influence of progesterone, its function changes based on stage of follicle cycle
- ovulation = abundance of watery mucous secretions to aid in sperm movement
- luteal phase = more viscous mucous which hinders sperm movement
- during pregnancy = glands proliferate and secrete super vicious mucous which forms a “mucus plug” preventing any sperm enters
Vagina
Contains 3 layers
1) mucosa = stratified squamous epithelium with basal epithelial cells synthesizing and storing glycogen in response to estrogen.
- this glycogen is released during normal desquamation which is then converted by lactobacillus into lactic acid which decreases pH of vagina (protective measure)
- also contains lamina propria = CT rich with elastic fibers and contains numerous lymphocytes and neutrophils
2) muscularis = smooth muscle bundles with circular configuration being closure to the mucosa and longitudinal bundles being closer to the adventitia
3) adventitia = CT rich layer with elastic fibers that allow for fetus to get through via stretching
mucus secretions in vagina during non arosual states = cervical glands. During arousal = greater and lesser vestibular glands
Greater vestibular gland
Opens near the posterior region oft he vaginal office and are homologous to the bulbourethral glands in males
Lesser vestibular gland
“Paraurethral glands”
Open near the anterior region of the vaginal orifice and are close to the external urethral orifice
- are homologous to the prostate in males
Labia majora
Folds of skin with hair follicles on the anterior portion fo the pelvis in females
- is homologous with the scrotum in males
Polycystic ovary syndrome (PCOS)
Enlarged ovaries with numerous cysts that caused on ovaries to reach maturation successfully
- also shows hyperandrogenism and oligoovulation
Is a very common cause of infertility in women
Diagnosis is made of exclusion of the following disorders
- CAH
- acromegaly
- hypothyroidism
- any pituitary issue
Clincial features
- virilization and voice changes**
- menstrual irregularities
- metabolic syndrome (especially obesity)
- acantholysis nicricans
- alopecia
- psychiatric conditions
Diagnosis: (needs 2 out of 3 after ruling out pother causes of irregular menstration and hyperandrogenism)
- hyperandrogenism (LH;FSH ratio >2:1); (increased total and fee testosterone
- an ovulation
- enlarged polycystic ovaries
Treatment
1st line for infertility = ovulation induction with letrozole OR clomiphene (inhbits estrogen receptors so no negative feedback)
1st line for virulization and hirsutism = oral contraceptive therapies with spironolactone, finasteride, or flutamide)
Follicular cysts
Are thin-walled fluid filled structures with both granulosa and thecal cells
- are made from late primary, antral or sometimes Graafian folicles which dont release the oocyte
Msot common cause of ovarian masss in women
Are usually benign but can produce high estrogen levels = menstrual irregularities
- also sometimes can disrupt blood vessels which produces hemorrhagic cysts
Clincial features
- usually asymptomatic
- can produce menorrhagia if endometriosis cysts
- can produce hyperandrogenism if corpus luteum cysts
- *can rupture, most common to rupture = corpus luteum cysts**
- Presents with sudden-onset unilateral lower abdominal pain with N/V possible.
- if severe rupture = hypovolemic shock
Diagnosis = pelvic US if not ruptured
- ruptured = B-hCG levels will be very high
Treatment = usually just watch
- if pain = NSAID
- if complications or NSAID refractory = surgery
Salpingitis
Is a subset of pelvic infalmmatory disease where the Fallopian tubes become inflammed/infected
Endometriosis
A benign chronic disease in women of reproductive age that is caused by endometrial tissue getting outside the uterus (ovaries are most common site)
- is believed to be caused by retrograde menstruation
Will affect the menstrual cycle and fertility though since this tissue still responds to estrogen
Can cause symptoms though
- dysmenorrhea
- dyspareunia
- chronic pelvic pain
- infertility
- dyschezia (pain while deficating)
Diagnosis
- PE = adnexal masses and rectovaginal tenderness
- translational US = enlarged uterus and evidence of ovarian cysts (chocolate cysts)
- laparoscopy = confirmatory test
Treatment
- pelvic pain = NSAIDs and hormonal contraceptives (remove contraceptives if they want to get pregnant)
- severe symptoms = continuous GnRH agonists w/ estrogen-progestin OCPs (to inhibit estrogen release and the proper menstrual cycle)
- surgeries therapy = laparoscopic excision and ablation (if wanting to get pregnant) and hysterectomy (if not wanting to get pregnant)
Fibrioids/Leiomyomas
IU
Placenta Previa
Occurs when the embryo attaches to the uterus near the internal os
- this results in the placenta being stuck in the cervix -> vagina opening and preventing the fetus to be able to move during parturition
Clinical features:
- sudden PAINLESS bright red vaginal bleeding (usually during the 3rd trimester)
- the uterus is soft and non tender and the fetus is usually in no distress
Risk factors
- > 35 yrs old and pregnant
- short intervals between pregnancies
- previous C-sections
- previous abortions or placenta previa
Diagnostics:
- transvaginal US
- NEVER do a digital vaginal examination for any unknown hemorrhage!!
Treatment
- if under 37 weeks gestational age = stabilize and prep for near future C-section
- if over 37 weeks gestational age = immediate C-section
- *always requires a cesarean section and must be caught ahead of time (fetus will die if undergoes normal birth)**
- also if normal birth = high risk for hemorrhage from mother
Cervical cancer
One of the most common female cancers and occurs usually near the internal os
The Pap smear test uses cells that are scraped from two sections of the uterus to determine potential precancerous lesions
Most common type occurs roughly at age 54 and is heavily linked to HPV
Atrophic vaginitis
Involves thing or atrophy of the vaginal epithelium caused by diminished estrogen levels and occurs most often in post menopause
key feature = low estrogen!
Clincial features
- decreasing labial fat pad
- vaginal soreness/dryness
- dyspareunia
- discharge and occasional spotting
- receding pubic hairs
Treatment:
- vaginal estrogen or systemic hormones therapies
These changes lead to frequent inflammation and infections, although primary SCC of the vagina in atrophic areas is almost never primary if present
Breast cancer
Is almost always derived from epithelial cells in the terminal lobules of mammillary glands
Most common form = invasive ductal carcinoma
Treatment is usually mastectomy and axillary lymph node resection if believed to be high grade
- low grade may just not targeted chemo/radiation
Breast and mammary glands
Originate from surface ectoderm along two ventral lines
During puberty in females = estrogen in high levels promote growth and proliferation of breast tissue as well as elongation and branching of ducts
Lobes = 15-25 per mammary gland and are classified as a compound tubuloalveolar gland
- each lobe is drained by a single lactiferous duct
- contains multiple lobules which all have terminal ducts that empty into the lactiferous duct
Lactation and pregnancy
Mammary glands grow during pregnancy and lactation development initiates
- primarily estrogen, progesterone and prolactin controlled
Late in pregnancy prolactin promotes secretion and accumulation of colostrum (protein, IgA and leukocyte rich fluid) that is synthesized by plasma cells
- this is what provides a passive acquired immunity to newborns
Following parturition, the prolactin really kicks into gear breast milk production
- protiens synthesis ramps up and are packaged into secretory vesicles which are released into the lumen via merocrine secretion (contains casein, B-lactoglobulin and a-lactoalbumin) also contains lipid droplets
- lactose is synthesized by the Golgi apparatus and secreted bonded to lactalbumin (major energy source for infant)
Suckling of the nipple promotes oxytocin secretion from the neurohypophysis (milk-ejection reflex)
