Female Reproductive Histology Flashcards
Examples of causes of female factor infertility?
Label this image of the female reproductive system.
-Uterine/fallopian tube
-Cervix = neck of uterus
How does a fertilised egg (zygote) move?
- In ovulation tertiary Graafian/mature follicle moves from ovaries into fallopian tube
- Fertilisation occurs @ ampulla of oviduct (fallopian tube) - specifically @ the ampullary-isthmic junction (this is where ovum & sperm are simultaneously transported)
- Implants into uterine endometrium - blastocyst implants into uterus!
- Embryo develops in uterus
How are the ovary & fallopian tube linked?
Ovary & fallopian tube = in close proximity & held together by broad ligament but not directly connected
Label.
Label.
What tissue is the clitoris formed from?
Erectile tissue
x2 corpora cavernosa
= erectile tissue
What tissue is the bulb of vestibule/in each of the labia minora formed from?
Corpora spongiosum
= erectile tissue
Difference between male & female erectile tissue?
In females - urethra DOES NOT pass through erectile tissue (but in males it does)
Structure of ovary - & what this looks like as histological cross-section?
-Germinal ep covering = single layer of ep = name = misnomer - as no germ cells (oocytes here)
-Hilum (H) = site of vs entry/exit
-Medulla (M) = inner part
-Cortex (C) = outer part -> contains gametes & support cells (= stroma)
-Contains oocyte within follicles (dormant until puberty)
What is the hypothalamic-pituitary-ovarian cycle?
- Hypothalamus secretes GnRH - pulsative nature of GnRH
- GnRH travels down to anterior pituitary gland & binds to receptors
- = promotes release of LH & FSH from ant. pit gland - secretion levels dependent on freq of impulses from GnRH
- LH & FSH travel in bloodstream to ovaries
- LH & FSH bind to ovaries = stimulates production of oestrogen & inhibin:
-Oestrogen –> helps regulate menstrual cycle & is essential component in other physiological processes
-Inhibin –> inhibits activin - usually responsible for stimulating GnRH production
-FSH –> also stimulates the development of ovarian follicles –> follicle most sensitive to FSH - becomes dominant Graafian follicle
-LH –> converts Graafian follicle into corpus luteum – which begins to produce progesterone
-Progesterone stimulates endometrium to become receptive to implantation of a fertilised ovum - Increasing levels of oestrogen, progesterone & inhibin have a -ve feedback effect on pituitary & hypothalamus
- = leads to decreased production of GnRH, LH & FSH
- = results in decreased production of oestrogen & inhibin
- If woman becomes pregnant - GnRH, FSH & LH remain inhibited = ceases menstruation
What is the menstrual cycle?
Cycle that occurs in uterus = to uterine wall – governs preparation & maintenance of uterus lining
–> uterine cycle = menstrual cycle
-Menstruation = shedding of endometrial lining of uterus
What is the ovarian cycle?
Cycle that occurs in ovaries – governs preparation of endocrine tissue & release of eggs – involves hormone release, follicle development & ovulation
Describe the uterine/menstrual cycle - & describe the events that occur is fertilisation takes place.
Follicular Phase
1. FSH levels rise = stimulates few ovarian follicles
2. Maturing follicles compete for dominance
3.1st follicle to fully mature produce oestrogen
–> FSH stimulates oestrogen production!
4. Oestrogen inhibits other competing follicles growing
5. Single follicle reaching full maturity = called Graafian follicle (oocyte develops within this)
6. Graafian follicle continues secreting increasing oestrogen amounts
7. Increasing circulating oestrogen results in:
- endometrial thickening
- thinning of cervical mucus = allows easier passage of sperm
- inhibits LH production by pituitary gland
8. Rising oestrogen levels exceed threshold level -so now conversely stimulate LH production = resulting in spike in LH levels ~ day 12
9. High LH causes thinning of Graafian follicle memb
10. Within 24-48 hours of LH surge - follicle ruptures = releases secondary oocyte
11. Secondary oocyte matures -> into ootid -> mature into mature ovum
12. Mature ovum - released into peritoneal space - taken into fallopian tube via fimbriae (finger-like projections)
= this is ovulation (stimulated by LH!)
Luteal Phase
13. After ovulation - LH & FSH stimulate remaining Graafian follicle to develop into corpus luteum
14. Corpus luteum produces progesterone
15. Increased progesterone levels result in:
- endometrium becoming receptive to implantation of blastocyst
- -ve feedback causing decreased LH & FSH (need both to maintain corpus luteum)
- increase in basal body temp
16. Levels of FSH & LH decrease = corpus luteum degenerates
17. Degeneration of corpus luteum causes loss of progesterone production
18. Decreasing level of progesterone triggers menstruation & cycle begins again
WHAT IF FERTILISATION OCCURS?
19. If ovum is fertilised - produces hCG (similar function to LH)
20. hCG prevents corpus luteum degenerating (causes continued progesterone production)
21. Continued production of progesterone prevents menstruation
22. Placenta takes over role of corpus luteum (from 8 weeks gestation)
Describe the ovarian cycle.
Proliferative Phase
-Endometrium exposed to increasing oestrogen levels due to FSH & LH stimulating oestrogen production
-Oestrogen stimulates repair & growth of functional endometrial layer (THICKENING OF UTERUS LINING) allowing recovery from recent menstruation (increasing endometrial thickness, vascularity & number of secretory glands)
Secretory Phase
= after ovulation has occurred
-Driven by progesterone produced by corpus luteum
–> results in secretion of substances by endometrial glands = makes uterus more welcoming environment for embryo to implant
Menstrual Phase
-At end of luteal phase - corpus luteum degenerates (if no implantation)
-Loss of corpus luteum causes - decreased progesterone production
-Decreasing progesterone - cause spiral arteries in functional endometrium to contract
-Loss of blood supply causes functional endometrium to become ischaemic & necrotic
–> so - functional endometrium sheds & exits through vagina as menstruation
Summarise the uterine/menstrual & ovarian cycles together.
Menstrual cycle = days 1-4
-Unused tissue breaks down into bloody discharge = menstruation – endometrium lining sheds – breakdown of uterus lining
*Low oestrogen & progesterone
*Low LH & FSH
Follicular phase - days 4-14
-FSH = stimulates ovaries to produce oestrogen
-Oestrogen causes uterus lining to thicken
-Oestrogen stimulates release LH & inhibits FSH release
–> so lining of uterus stimulated by oestrogen – thickens (in preparation for possible reproduction) – occurs at same time as follicle development
-LH = stimulates ovulation
–> leads to single dominant follicle – which releases its oocyte during ovulation
*FSH = causes surge in oestrogen
*LH surge = causes ovulation (ovary releases ovum into fallopian tube) - day 12/13
Luteal phase - days 14-28
- After ovulation - LH & FSH stimulate remaining Graafian follicle to develop into corpus luteum
-Corpus luteum produces progesterone (stimulated by LH) ###
-Progesterone - acts on endometrium – builds up tissues with enriched blood supply & inc glandular secretions – to nourish future embryo-
-Progesterone = inhibits LH (& FSH?) production ### - feedback loop???
-LH & FSH decrease = causes corpus luteum degeneration
-Corpus luteum degeneration = decreases progesterone levels (as CL produces P)**
–> this is if is NO FERTILISATION = corpus luteum stops producing progesterone**
*Oestrogen still high(ish) & progesterone - until P decreases
Basics of the uterine cycle?
Give the sequence of ovarian follicular development.
-Girls = born with all of their primordial follicles = finite number - but lay dormant until puberty
-Puberty = onset of menstrual cycle
–> a few of these primordial follicles begin to mature into primary & secondary follicles = competing for dominance
-1st follicle to become secondary follicle = ‘selected’ - will produce oestrogen (due to FSH)
-Oestrogen inhibits other competing follicles growing
-Single follicle reaching full maturity = Graafian follicle (oocyte develops within this)
-Graafian follicle = ovulated - the oocyte is ovulated!!! (ovary -> f tube)
Lutenisation:
- After ovulation - LH & FSH stimulate remaining Graafian follicle to develop into corpus luteum
-Corpus luteum produces progesterone
-Progesterone - thickens endometrium
-Progesterone = inhibits LH & FSH production
-LH & FSH decrease = causes corpus luteum degeneration
-Corpus luteum degeneration = decreases progesterone levels (as CL produces P)**
–> this is if is NO FERTILISATION = corpus luteum stops producing progesterone**
Oestrogen still high(ish) & progesterone - until P decreases
** Degenerated corpus luteum = corpus albicans = scar tissue left over = white in colour
What are the 5 components that can be seen in follicles at some point during maturation?
-Oocyte (in follicle)
-Zona pellucida (outer covering of follicle)
-Granulosa cells (support cells)
-Theca cells (support cells)
-Antral cavity (fluid filled)
Name the 4 stages of follicular development in terms of general terms & antral terms.
What is the female germ cell?
Oocyte
Describe formation of primordial follicles in female embryos.
Oogonia = small diploid cells
–> mature into primordial follicles in a female foetus OR the female (haploid or diploid)
-So -> follicles develop during embryogenesis
–> all formed by 2nd trimester of pregnancy - found in ovaries of embryo
Features of primordial follicles -> within the ovary?
-Germinal epithelium of ovary (remember - this is not where germ cells i.e., oocytes are actually found!) = E
-Mesenchymal stroma of ovary (which is embryonic CT - gives ovary its cellular framework) = S
-Primordial germ cell = G (1st image)
–> has dark pink circle w/ white ring around - which has dark purple circles in it
*dark pink circle = oocyte = O
*dark purple circles in white ring = granulosa cells (support cells) = G (2nd image)
-Primordial follicle itself = made up of oocyte & granulosa cells!
What leads to primordial follicles forming primary follicles?
Start of menstrual cycle - due to onset of puberty
–> some follicles recruited into growing pool & matured - 1st one(s) to FULLY mature will be menstruated
Features of primary follicles -> in the ovary?
-Oocyte = O
-Granulosa cells (support cells) = G -> thickens - more layers in the ring around oocyte (from primordial to primary)
-Zona pellucida = ZP -> has now developed
What is the zona pellucida?
-Glycoprotein coat of oocyte
-Sperm MUST penetrate to enter oocyte (fertilisation)
Features of secondary follicles -> in the ovary?
O: Oocyte
ZP: Zona Pellucida (oocyte coating)
G: Granulosa cells (support cells & are secretory - found in rim around oocyte)
TI: Theca interna (spindle) - (support cells)
TE: Theca externa (plump)
C: Antral Cavity (filled with supportive fluid)
Theca (= support cells) differentiates into x2 layers:
-Theca interna (rounded cells - secrete androgens & follicular fluid)
-Theca externa – (spindle shaped cells, more fibrous)
–> all features that can be in follicle are seen in secondary follicle
What leads to secondary follicle becoming -> tertiary/Graafian follicle?
-Antral cavity enlarges - forms ANTRUM
-Granulosa cells separating antrum & oocyte -> form cumulus-oocyte-complex
–> cumulus cells = granulosa cells around oocyte (as also have granulosa cells NOT around oocyte)
-Cumulus cells degenerate - forms corona radiata
Describe the process of ovulation - OOCYTES!?!
(Oocytes are ovulated - not the whole follicle!)
- Primary oocytes undergo meiosis I in foetus - but meiosis is then paused
- Primary oocyte becomes -> secondary oocyte:
-> Primary oocyte - completes meiosis I (just before ovulation)
= 23 chromosomes remain (so is haploid) & other 23 go off to side to form polar body
= now a secondary oocyte w/ polar body & meiosis is again paused
(Secondary & tertiary follicles involved here - contain ALL features of follicles!) - Tertiary follicle ruptures (don’t get tertiary oocyte!)
–> secondary oocyte & its surrounding cumulus cells are released = ovulation
–> meiosis II then starts (after ovulation) & then pauses - Oocyte & cumulus move from ovary into fallopian tube
- Tertiary/graafian follicle becomes corpus luteum (which will either remain if fertilisation occurs or will form corpus albicans if not)
- If fertilisation occurs to the ovulated oocyte:
–> meiosis II is then completed = forms another polar body (so have x2 polar bodies)
Name the process that occurs after ovulation - to the remaining follicle.
Luteinisation
Process of luteinisation?
- Corpus hemorrhagicum (“bleeding corpus luteum”) = temporary structure formed immediately after ovulation from ovarian follicle as it collapses & fills with blood which rapidly clots
- Forms corpus luteum (‘yellow body’) - produces progesterone (i.e., is steroidogenic) for ~14 days (which inhibits LH & FSH)
- Forms corpus albicans (white) = small fibrous mass - formed by break down of corpus luteum
-Corpus luteum stops producing progesterone
-Progesterone inhibits LH & FSH production
-Decrease in LH & FSH - causes corpus luteum degeneration (by macrophages)
-At same time - fibroblasts lay down type I collagen -> forms corpus albicans
***This = luteolysis - loss of function of corpus luteum - Corpus albicans may form scar on ovary surface
==> this all only occurs if is NO fertilisation! -> if there is fertilisation - then corpus luteum remains - until placenta takes over steroidogenesis!!!
Describe what happens to the corpus luteum if fertilisation occurs - if woman becomes pregnant SUCCESSFULLY?
Corpus luteum remains steroidogenic (producing hormones - progesterone?) until placenta takes over @ week 13 gestation
Features of corpus luteum?
= Yellow body
-Blood clots fill lumen
-Granulosa & theca interna cells are lutenised
–> after rupture of mature ovarian follicle - granulosa & theca interna cells differentiate into the granulosa lutein & theca lutein cells of corpus luteum
Features of corpus albicans?
= White body
-Oval mass of fibrous tissue
-Fibroblasts & theca externa cells -> produce & lay down type I collagen = replaces lutein cells = forms corpus albicans
-> so is non-steroidogenic (as replaces lutein cells)
-Scar tissue (remains in ovary permenantly)
Summarise follicular development - what each stage is & what the ovary features are.
Label this image of the fallopian/uterine tube.
What are the 4 LAYERS of the fallopian/uterine tube?
*4 layers - most inner to most outer:
-Mucosa (tall columnar epithelium)
-Submucosa
-Muscularis (inner circular & outer longitudinal = smooth muscle)
-Serosa
= makes up walls of fallopian tubes
***Different proportion of mucosa to smooth muscle relative to it regional functions
–> thicker smooth muscle layer & thinner mucosa layer @ start at uterus end of tube compared to ovarian end
What are the layers seen in the ampulla of the fallopian tube & what is the structure of this region?
-V. folded ep = inc SA
-Less smooth muscle (contraction - less important for transport)
Structure of the epithelium of fallopian tube?
Epithelium = tall columnar
-Highly folded
-Contains secretory & ciliated cells
–> secretions = mucin
What can alter the speed of oocyte transport & secretion production?
Contractions & cilia ‘beating’
-Speeded up by: (increased) oestrogen
-Slowed down by: (increased) progesterone
Secretions for oocyte
-Increased by (increased) oestrogen
Secretions for embryo
-Increased by (increased) progesterone
Summarise the structures & functions of fallopian tube.
Stages of the uterine cycle - what happens in each?
-Shed the functional layer of endometrium
Define menses.
Shedding of functional layer of endometrium
-> associated with muscle spasms & pain
What are the layers of the uterus?
- Endometrium:
-Stratum compactum (C)
-Stratum spongiosum (S)
-Stratum basalis (B) - Myometrium = consists of smooth muscle layes
- Perimetrium
Number of layers of myometrial smooth muscle?
3
What layers of the uterus are shed during menses - days 0-5?
Functional zone of the endometrium:
-Stratum compactum
-Stratum spongiosum
What stimulates the proliferate phase of uterine cycle (i.e., what stimulates regrowth of endometrium) - days 5-14?
Oestrogen promotes cell proliferation of basal layer to regenerate endometrial lining
What happens during the secretory phase (i.e., to prepare uterine lining for implantation) - days 14-28?
- Progesterone inhibits further endometrial growth
- Induces differentiation of epithelium & stroma in preparation for decidualisation
Early in secretory phase subnuclear vacuoles appear (V) - then glands become corkscrewed & become full of secretion (SE)
What happens in shedding process in menses - menstrual phase - days 0-5?
Functional layer (stratum functionalis = stratum compactum & spongiosum) of endometrium undergoes apoptosis
–> due to decrease in progesterone levels
–> causes leakage of blood
What is found in the uterus endometrium - structures with a purpose?
-Uterine glands
-Spiral arteries
–> for successful implantation & for supporting embryo
When do women undergo routine cervical screening - UK?
Aged 25-64
What is the internal os?
Junction between uterine body & cervix
- i.e., the internal opening leading to uterus
What is the external os?
Where lumen of cervix opens into vaginal cavity
- i.e., an external opening leading to vagina – marks transition from ectocervix to endocervix
What/where is the ectocervix?
Protruded into vagina
Epithelium of ectocervix & what else lines the ectocervix?
Stratified squamous non-keratinised ep
-Rich glycogen
What/where is the endocervix?
Lumen of cervix - (luminal portion)
-Continuous with uterine body proximally
= yellow on image!!!
Epithelium of endocervix/endocervical canal?
Simple (tall) columnar mucus-secreting ep
Summarise relationship between ectocervix, endocervical canal & external Os & internal Os.
Ectocervix =
-Portion of cervix that projects into vagina
-Ep = stratified squamous non-keratinised
-External os = opening in ectocervix (marks transition from ectocervix to endocervical canal)
Endocervical canal
-More proximal &‘inner’ part of cervix
-Ep = mucus-secreting simple columnar
-Internal Os = where endocervical canal ends & uterine cavity begins
Structure of endocervical canal that makes its epithelium mucus-secreting?
-Ep contains gland-like structures
–> but are actually invaginations (I) of epithelium into crypts
= gives large SA to produce ‘cervical mucus’ - which then fills endocervical canal
Explain how the cervix is able to both act as a barrier to pathogens but also allow passage of sperm.
-> due to hormonal changes
*High Oestrogen (before ovulation!!!)
-Mucus plug becomes thin, watery & full of electrolytes (high spinbarkeit)
=> so sperm can penetrate/pass through mucus plug
*High progesterone (after ovulation!!!)
-Mucus plug becomes thick & viscid (low spinbarkeit)
=> so sperm cannot penetrate/pass through mucus plug
What is the cervical stroma composed of?
-Smooth muscle fibres
-Collagen
Ratio of collagen : smooth muscle - may increase with age - associated with increased risk during childbirth
What happens to the cervix at puberty?
= ectropion (= the protrusion part…)
1. Cells that were in endocervical canal protrude out into vaginal canal –> caused by oestrogen
= endocervical epithelium extends distally into acid env of vagina & forms an ectropion
–> so these cells can survive the acidic env of vaginal canal
- These cells undergo transformation (forming transformation zone) from simple columnar of endocervical canal to the vaginal ep (stratified squamous non-keratinised) -> i.e., squamous epithelium regrows over ectropion
(Openings of crypts may be obliterated in process - forms mucus-filled Nabothian follicles)
-Ectocervix remains throughout this!
4 layers of the vagina?
1 = Stratified squamous epithelium
2 = Elastin rich submucosa
3 = Fibromuscular layer (ill-defined)
4 = Adventitia
