Histology - Lecture 25 - Female Reproductive System Flashcards
3 functions of the female reproduction system?
- Exocrine: produce ova (ovaries)2. Endocrine: produce female hormones responsible for the production of germ cells, for the maintenance of accessory organs, and for secondary sex characteristics (ovaries mainly)3. Nurture of infants
What are the 3 major anatomical components of the female reproductive system?
- Internal organs: 2 ovaries, 2 uterine tubes, the uterus and the vagina2. External genitalia: labia minora, labia majora, clitoris, vestibular glands3. Mammary glands
Why are mammary glands considered part of the reproductive system?
Because they are under endocrine control and further develop during pregnancy
What are the primary female sex organs?
Gonads = ovaries
2 other names for female germ cells?
Oocytes = gametes
What are the 3 age related changes in function of the female reproductive system?
- Menarche: first menses, initiation of pubertal development (~12-13 year old)2. Menstrual cycle: cyclic appearance of menses associated with fertility3. Menopause: cyclic nature of the tract becomes irregular and eventually disappears in favor of a tonic status (~50 year old)
List and describe the 4 layers of the ovary. What layer is the major site of ovarian cancer?
- *Outer layer: simple squamous/cuboidal/columnar germinal epithelium (misnomer)2. Tunica albuginea: dense connective tissue3. Cortex: containing the ovarian follicles in various stages of development4. Medulla: occupies the central region of the ovary and consists of blood vessels and connective tissue
List the 8 stages of follicular development in the cortex of the ovary.
- Primordial follicles2. Primary unilaminar follicles 3. Primary multilaminar follicles 4. Secondary follicles 5. Graffian follicles6. Corpus luteum7. Corpus albicans8. Atretic follicles
How many primordial follicles at birth?
2 M
Describe primordial follicles.
Primary oocyte arrested in meiotic prophase I, dictyotene stage, surrounded by a layer of flattened follicular cells, which are surrounded by stromal cells
Have primordial follicles responded to FSH?
NOPE
What happens to primordial follicles at puberty?
Secretion of FSH => stimulates groups of follicles to undergo development and produce estrogen and their follicular cells acquire more FSH receptors and become more columnar => now called granulosa cells
Where does meiosis of primary follicles start?
In utero
Where are LH and FSH secreted from?
Anterior pituitary: pars distalis and pars tuberalis
How many primordial follicles respond to FSH every 28 days?
Up to 20 primordial follicles
Describe primary unilaminar follicles.
Primary oocyte surrounded by one (unilaminar) layer of granulosa cells
During what follicular stage does the zona pellucida start forming?
Primary unilaminar follicle
Describe primary multilaminar follicles.
- Primary oocyte surrounded by more than one (multilaminar) layers of granulosa cells 2. Granulosa cells and the oocyte together deposit an extracellular coat, the zona pellucida onto the primary oocyte, which is traversed by delicate cytoplasmic processes from the granulosa cells (filopodia) and microvilli projecting from the oocyte3. Stromal cells differentiate to form the theca interna
Describe secondary follicles.
- Identified by the presence of an antrum (cavity) formed from accumulations of hyaluronic acid-rich fluid (follicular liquor)2. Theca further differentiates into a theca interna and a theca externa
Other name for secondary follicles.
Antral follicles
During what stage(s) of follicular development is the first meiotic division complete?
Around the time of the transition from primary multilaminar to secondary follicle
What does the follicular liquor of secondary follicles contain? Role?
Oocyte meiosis inhibitor (OMI) that maintains arrest of the oocyte in meiotic prophase II (dictyate stage)
What does the theca interna of secondary follicles consist of?
Cells are steroidogenic producing androstenedione/testosterone, which is an intermediary of steroidogenesis and diffuses into the follicle proper to be metabolized by the granulosa cells into estrogen+ they have capillaries to facilitate the diffusion of steroids throughout the body+ liquid droplets (typical of steroid producing cells)
What does the theca externa of secondary follicles consist of?
Consists mainly of connective tissue
Describe Graafian follicles.
- Contains a very large antrum filled with follicular liquor 2. Oocyte that is eccentrically located and connected to a layer of granulosa cells that line the inner aspect of the mature follicle by a pedicle of granulosa cells3. Corona radiata: inner most single layer of granulosa cells surrounding the oocyte that are more tightly packed together4. Cumulus oophorus: several more accumulations of granulosa cells outside of the corona radiata continuous with the pedicle
During what follicular stage is the occyte arrested in the dictyate stage?
Secondary follicle
During what meiotic stage does ovulation happen?
Metaphase II
How many secondary follicles become a Graafian follicle? What happens to the rest of the 20?
JUST ONECould stay arrested and develop later or could die (become atretic)
Other names for Graafian follicle?
Mature follicle = tertiary follicle
During what follicular stage does ovulation occur?
Graafian follicle
Describe ovulation of the Graffian follicle.
Dominant follicle bulges from the surface of the ovary => LH surge => follicle produces local progesterone that is sequestered inside the follicle => stimulation of proteolytic enzymes (e.g. collagenase) to weaken the follicular wall + movement of fluid into the follicle via prostaglanding secretion => LH overrides the action of OMI => resumption of meiosis from prophase II to metaphase II + follicle swelling and rupture dispersing OMI => ovulation occurs and ovum is expelled into the peritoneal cavity
What precisely causes the ovulation of the Graafian follicle?
Enzymatic dissolution of the connective tissue (not increase in pressure)
What happens to the corona radiata and cumulus oophorus upon ovulation?
Remains attached to the ovum following ovulation and even following fertilization
What DIRECTLY surrounds the oocyte following ovulation?
Zona pellucida
Other name for corpus luteum?
Yellow body
Describe atretic follicles.
Partially developed follicles become developmentally arrested and degenerate:- detachment of granulosa cells- death of the oocyte, which is no longer oval shape but wobbly instead- formation of pycnotic (dark) bodies- apoptosis
When does follicular atresia occur (development of atretic follicles)? What to note?
From the time of birth until menopauseNote: most prominent just after birth and during pregnancy
Why do some follicles become atretic?
Natural selection
Describe the corpus luteum.
Formed after ovulation from the remnants of the ruptured graffian follicle: 1. Follicular fluid is lost resulting in the collapse of the follicular wall forming a pleated corpus luteum 3. Granulosa lutein cells: under the influence of LH from the anterior pituitary, the granulosa cells of the former Graafian follicle become enlarged, occupy most of the space of the corpus luteum and secrete progesterone4. Theca lutein cells: former theca interna of the Graffian follicle become small darkly staining lutein cells and now produce estrogen
Role of theca and granulosa lutein?
Form a temporary endocrine gland whereby elevated progesterone and estrogen prevent development of any new follicles and prevent ovulation for the remainder of that cycle because cause continuous negative feedback to the hypothalamus-pituitary axis to inhibit LH/FSH secretion and surge, thus inhibiting ovulation
What is the basis of the contraceptive pill?
Progesterone and/or estrogen prevent development of any new follicles and prevent ovulation just like the corpus luteum after ovulation because cause continuous negative feedback to the hypothalamus-pituitary axis to inhibit LH/FSH secretion and surge, thus inhibiting ovulation
What happens to the corpus luteum if pregnancy does not occur 2 weeks post-ovulation?
Progesterone from the granulosa lutein cells negatively feeds back to the pituitary => reduced LH secretion => degeneration of the corpus luteum into a corpus albicans => degenerates by autolysis and phagocytosis by macrophages
What happens to the corpus luteum if pregnancy occurs within 2 weeks post-ovulation?
Corpus luteum is rescued from degeneration by chorionic gonadotrophin (hCG) produced by the placenta, which is homologous to LH and promotes estrogen and progesterone secretion
Consequence of phagocytosis of corpus albicans?
Residual scar of connective tissue that results from the absorptive process may take years to completely disappear
Other name for primary multilaminar follicle in development?
Pre-antral follicle
Purpose of zona pellucida?
Block to polyspermy
What separates the granulosa layer of the secondary follicle from the theca interna?
Basement membrane
Does ovulation of the ovary happen on the right or left side?
Alternates from month to month
What does the corpus albicans consist of?
Cytoskeletal elements, proteins, extracellular matrix components
What happens to the infundibulum around ovulation?
Its fimbriae move around in a manner to trap and draw the ovum into the opening of the infundibulum
Where does fertilization occur?
Ampulla of uterine tube
What can lead to multiple concurrent pregnancies?
LH injections because they can induce multiple ovulations
What does reduced ovulation mean?
Reduced fertility
List the 3 layers of the wall of the oviduct. Describe each.
- Mucosa with folds lined with simple cuboidal to low columnar epithelium with two cells types, secretory cells (non-ciliated) and ciliated cells, which are both estrogen dependent => ciliated cells help move the ovum through the oviduct, whereas the secretory cells secrete proteins to nurture a potential zygote + underlying lamina propria (connective tissue)2. Muscularis: inner circular and outer longitudinal layer3. Serosa of visceral peritoneum: connective tissue connected to the broad ligament of the uterus
Where are uterine tube mucosal folds most prominent?
Ampulla and decrease in height and length toward to isthmus
What moves the ovum through the fallopian tube?
- Peristaltic contractions of the muscularis 2. Beating motion of the ciliated cells
What is the ovum surrounded by in the uterine tube? Implication?
Suspended in a viscous oviductal fluid formed by transudation from the surrounding vasculature and by estrogen stimulated secretion from the secretory cells of the wall of the fallopian tube => fluid forms an essential environment for fertilization
What can stop the secretory activity of the secretory cells of the wall of the uterine tube?
Progesterone
Where does the oviductal fluid accumulate the most?
Four times as much fluid accumulates in the ampulla than the isthmus
How much time does it take sperm to be transported from their site of deposition to the ampulla?
~2 hrs
For how long can the fallopian tube support the development of the blastocyst?
1 week post-ovulation
What happens to the lamina propria of the uterine wall during an ectopic pregnancy?
It reacts like the endometrium forming decidual cells
What is the uterine ostium?
Opening for passage from cervix to vagina
What are the 3 layers of the uterus? Which is thickest?
- Endometrium2. *Myometrium 3. Perimetrium
Other than secreting proteins, what is the other role of the secretory cells of the wall of the oviduct?
Filtration of blood borne components of capillaries in lamina propria to form the transudate of the oviductal fluid
Describe the endometrium of the uterus.
- Simple columnar epithelium with a mixture of ciliated cells and secretory cells 2. Lamina propria, the stroma, containing simple tubular glands (endometrial glands) that sometimes branch in their deeper portions near the myometrium
Which part of the uterus forms decidual cells during pregnancy?
The endometrial stroma between the glands
2 layers of uterus endometrium? Describe each.
- Functionalis: lost at menstruation2. Basalis: retained at menstruation
Which cells of the uterus endometrium provide the new epithelial cells of the uterus after menstruation?
The glandular cells of the endometrial basalis
Describe the vascular supply of the endometrium.
Arcuate arteries from the myometrium branch to form two sets of arteries:1. Straight arteries that supply the basalis 2. Coiled arteries that supply the functionalis
Describe the myometrium of the uterus.
Consists of smooth muscle cells interspersed by connective tissue
Changes to myometrium during pregnancy? What to note?
Smooth muscle cells undergo hypertrophy (increase in size) and hyperplasia (increase in number by cell division)Note: following birth enzymatic destruction of some of these cells reverses the growth
Describe the perimetrium of the uterus.
Constituted in different parts by:1. Outer adventitia composed of connective tissueOR 2. Serosa of connective tissue and mesothelial cells that form part of the broad ligament
How do we number the days of the menstrual cycle?
Starting from the 1st day of menstruation = day 0
Average menses?
4 days
What are the 3 phases of the menstrual cycle? Length for each?
- Proliferative phase: 9 days2. Secretory phase: 13 days 3. Ischemic phase: 6 days
2 other names for the proliferative phase of the menstrual cycle?
Estrogenic or follicular phase
Describe the proliferative phase of the menstrual cycle.
Gradual increase in estrogen from follicles stimulates:1. Proliferation of the endometrial basalis2. Elongation of the straight tubular glands (narrower lumen) 3. Increase in number of stromal cells 4. Growth of the coiled arteries into the uterine stroma OVERALL: endometrium doubles or triples in thickness
2 other names for secretory phase of the menstrual cycle?
Progestational or progravid (under influence of corpus luteum) phase
Describe the secretory phase of the menstrual cycle.
Estrogen from the theca lutein cells and progesterone from the granulosa lutein cells (MAIN EFFECT) cause:1. Endometrium thickens further in preparation for implantation2. Tubular glands become coiled and convoluted to:- increase surface area because the endometrium is secreting fluids in uterus to maintain potential viability of implanted zygote/nourish ovum (glycogen and mucopolysaccharides)- to dilate lumens of glands - to have edema (fluid retention) of the stroma for maximum thickness of the endometrium3. Spiral uterine arteries become coiled further
Other name for ischemic phase of the menstrual cycle?
Menstrual phase
Describe the ischemic phase of the menstrual cycle.
If implantation does not occur the corpus luteum begins to regress resulting in a marked decline of ovarian hormones (estrogen, progesterone mainly), which causes the functionalis to undergo sporadic episodes of cessation of its blood supply by constriction then dilation of the uterine spiral arteries and their retraction => intermittent hypoxia, ischemic necrosis and exfoliation of the functionalis => menstruation with bleeding to wash out necrotic tissue to prevent infections
Purpose of dating of the endometrium?
Assess the function of the ovary, and indirectly the hypothalamus and pituitary in cases of infertility
What can a shortened luteal phase of the ovarian cycle cause?
Infertility
What is endometriosis?
Condition in which tissue that normally grows inside the uterus (endometrium) grows outside it
Describe the early follicular phase of the ovarian cycle (3 steps). What menstrual cycle phase does this correspond to? How long does it last?
- FSH stimulates development of up to 20 preantral primary follicles = RECRUITMENT2. Only one of the follicles is selected to become the dominant secondary follicle 3. Day 6-8: follicle secretes estrogen, which exerts (-) feedback on FSH secretion and induces the proliferation of endometrium ISCHEMIC AND PROLIFERATIVE PHASES = 14 days
Describe the mid-follicular phase of the ovarian cycle (4 steps). What menstrual cycle phase does this correspond to?
- Estrogen levels reach and stay at 150 pg/mL for ~36 hrs2. Estrogen (+) feedback, large LH surge and slight FSH surge3. LH stimulates the follicle to secrete progesterone4. Progesterone induces ovulation by stimulating collagenolytic enzymes that weaken the wall of the secondary follicle causing rupture and release of ovumPROLIFERATIVE PHASE
Describe the luteal phase of the ovarian cycle (4 steps). What menstrual cycle phase does this correspond to? How long does it last?
- Remaining follicular remnant becomes corpus luteum2. Corpus luteum takes over secreting large amounts of estrogen and progesterone (theca and granulosa lutein cells) which continues to cause the development of the endometrium3. High progesterone levels inhibit the positive feedback action of estrogen on FSH and any new follicular development, reduces ciliary motion, and increases cervical viscosity4. 2 scenarios depending on whether fertilization happensSECRETORY PHASE = 14 days
Describe what happens during the luteal phase of the menstrual cycle if fertilization does not takes place.
- Corpus luteum degenerates (12 days after ovulation)2. Decrease of estrogen and progesterone lead to menses and no more (-) feedback on pituitary so FSH and LH increase3. New round of follicle stimulation in the ovary
Describe what happens during the luteal phase of the menstrual cycle if fertilization takes place.
- Mensus inhibited2. Stromal cells of the endometrium enlarge in response to increased progesterone3. Placenta secretes placental hCG, which replaces LH (binds to same receptors) and rescues corpus luteum4. Corpus luteum continues to supply progesterone to the uterus for first 2-3 months until the placenta takes over => corpus luteum placental shift
What does LH stand for?
Luteinizing hormone
What does FSH stand for?
Follicle-stimulating hormone
How long after ovulation must fertilization happen?
Within 24 hours
On what day of the menstrual cycle does ovulation occur?
Day 14
If fertilization occurs, when does hCG enter maternal circulation?
Once embryo implants
What is hCG? What to note?
Dimer peptide, with one of the dimers being almost identical to LH
What is the cervix lined by?
2 different types of epithelium: 1. Simple columnar epithelium that is highly folded into crypts (NOT GLANDS) within the endocervical canal 2. Stratified squamous non-keratinized epithelium on part outside of the cervix that projects into the vagina
Where exactly do cervical cancers most frequently arise? What do we call this?
Region of transition from the endocervical canal lined by simple columnar epithelium to the stratified squamous non-keratinized epithelium => it is the non-keratinized stratified squamous epithelium that gives rise to cervical cancer= transformation or junctional zone
How are cervical cancers checked for?
Papanicolou stain test (Pap smear)
What is cervical cancer often caused by?
HPV virus
Effect of ovarian cycle on cervix? Explain how.
- At ovulation the epithelium secretes an aqueous fluid that allows the sperm to penetrate the cervix for fertilization, due to estrogen action because it causes body water retention 2. In the luteal phase or during pregnancy the epithelium secretes a viscous fluid that prevents the penetration of sperm or microorganisms through the cervix to protect the potential presence of an implanting zygote
Other than cervical cancer, what other cancer can HPV cause?
Oral cancer (from oral sex)
3 layers of the vagina? Describe each
- Mucosa with non-keratinized stratified squamous epithelium similar to that lining the outer cervix + lamina propria 2. Muscularis: longitudinal bundles (rugae) and longitudinal smooth muscle fibers3. Adventitia: dense connective tissue and elastic fibers that attaches vagina to surrounding organs
Why are there increased vaginal infections after menopause?
Reduced estrogen levels result in a thinning of the vagina mucosa layer leading to increased infections
What layer of the vagina undergoes cyclic changes with the menstrual cycle?
Lamina propria of mucosa
Are there glands within the vagina?
NOPE
What are the 2 types of vestibular glands? Where are they located? Include type and epithelium of each.
- Glands of Bartholin: tubuloalveolar with simple columnar epithelium 2. Skene’s glands: tubuloalveolar with pseudostratified or simple columnar epitheliumOn each side of the vestibule
4 other names for Skene glands?
- Lesser vestibular glands2. Periurethral glands3. Paraurethral glands4. Prostata feminina
Purpose of Skene and Bartholin’s glands?
Secrete lubricating fluid for vagina
What are the labia minora? Epithelium? What to note?
Folds of skin with a core of spongy tissueKeratinized stratified squamous epithelium Note: primarily devoid of sebaceous glands and adipose tissue
What is the embryological equivalent to the penis?
Clitoris
What does the clitoris contain? Epithelium?
Contains venous spaces of erectile tissue, divided in the midline and surrounded by a connective capsuleStratified squamous keratinized epithelium
What is the female urethra lined by?
Pseudostratified columnar epithelium and/or stratified squamous epithelium at its exit from the body
What is the embryological equivalent to the prostate?
Skene glands
What is female circumcision?
Partial or total removal of the external genitalia or other injury to female genital organs for non-medical reasons: removal of clitoral hood and glans, inner labia, and in most severe cases removal of both labia and closure of vulva (infibulation)
Describe the development of mammary glands at puberty.
Rising estrogen levels + background of growth hormone and cortisol:1. Lactiferous ducts elongate and branch2. At the end of each small duct (terminal interlobular duct) a lobule is developed
What are mammary gland intralobular and interlobular ducts lined by?
Cuboidal to low columnar epithelial cellsIn the wider ducts these cells are arranged as a double layer
What happens to the mammary gland post-puberty?
- Substantial deposits of adipose tissue occurs between the interlobular connective tissue2. The interlobular ducts join to form lacteriferous ducts that empties into the nipple
Nipple epithelium?
Stratified squamous keratinized epithelium continuous with that of the adjacent skin
Describe the lactating mammary gland.
- Estrogen + progesterone + prolactin (because of estrogen) + growth hormone + cortisol => during pregnancy the duct system completes its development + secretory alveoli bud from the smallest intralobular branches + increased fat deposits => increased breast volume 2. By the end of pregnancy each secretory alveolus consists of a simple columnar epithelium, together with associated myoepithelial cells3. Milk is produced by the epithelial cells of the alveoli and accumulates in the lumen and the lactiferous ducts
Describe milk formation by the lactating mammary gland.
Milk formed as spherical droplets in the cytoplasm of the secretory cells where it passes out of the cell encompassed by remnants of the cytoplasm during apocrine secretions
Why do the milk droplets of the lactating mammary gland contain?
- Lipid2. Caseins3. Alpha-lactalbumin4. IgA (for maternal antibody acquisition by immunologically naïve infant) 5. Lactose
What is fibrocystic breast disease?
Benign disease whereby nodules arise from the stromal component of the breast tissue
Is breast cancer one of the most prevalent forms of cancer in women?
DUH.
Where does breast cancer arise?
Epithelial cells of the intralobular ducts (2/3) or the acini (1/3)
What is colostrum?
Milk droplets secreted by mammary glands
Main reason for follicular atresia?
Inappropriate meiosis
What is found at the base of cilia?
Basal bodies
Innervation of external genitalia?
Merve fibers, Meisners and Pacinian corpuscles are prevalent around the clitoris and elsewhere throughout the external genitalia contributing to arousal
What prevents the development of many secondary follicles into Graaffian follicles?
Theca interna grows faster in one of them and secretes local inhibitory factors to arrest the development of the other follicles causing them to become atretic and die
What happens to the theca and granulosa cells of the Graaffian follicle after ovulation that are ejected with the ovum?
They disintegrate in the peritoneal cavity
What hormone does the ovary primarily secrete before and after ovulation?
Before: estrogenAfter: progesterone
The length of which ovarian cycle phase is more constant: follicular or luteal?
Luteal, follicular phase is more variable in length
What does cervical mucous ferning refer to?
Refers to thinning of mucous during ovulation which causes a ferning pattern in histological preparation
If you were to the remove the transformation zone, would you be able to have cervical cancer?
NOPE
