Reproduction Week 1 Flashcards
1
Q
Where does the urogenital tract develop from?
A
Intermediate mesoderm
2
Q
Name and describe the three kidney structures involved in the development of the urinary system:
A
1) pronephros = 7-10 solid cell groups in cervical region, regresses by week 4 of development
2) mesonephros = develops in upper thoracic and upper lumbar regions, produces supporting cells for genital ridge, appears in week 4 after regression of pronephros
3) metanephros = the DEFINITE kidney that appears in week 5 and is functional by week 11.
- formed by two parts: metanephric cap and ureteric bud
3
Q
What is the cloaca?
A
Posterior orifice that acts as an opening for the intestinal/reproductive/urinary systems in early development.
Is made from hindgut with endodermal lining
4
Q
What is the ureteric bud?
A
A protrusion from the mesonephric duct that allows drainage of the developing kidney
5
Q
How is the bladder formed?
A
- cloaca is divided by the urorectal septum and fuses with the cloacal membrane (weeks 4-7)
- anterior urogenital sinus and porterior rectal canal formed
- bladder forms from cranial part of urogenital sinus
- bladder begins to get lined with endoderm
- the trigone of the bladder forms from caudal part of the mesonephric duct
6
Q
What is the allantois?
A
- sac-like outpouching of the hindgut involved in nutrition and excretion
7
Q
What is the urachus?
A
- called median umbilical ligament later in life
- is fibrous remnant of channel between the bladder and umbilicus that used to drain urine in foetal during 1t trimester
- forms from the allantois during weeks 5-7
8
Q
What are the three main steps in the formation of the genital system?
A
- Genital duct formation
- Gonad formation
- External genitalia formation
9
Q
How are the genital ducts formed?
A
- 2 pairs of genital ducts form in weeks 5-6
- paramesonephric ducts (müllerian ducts) are more lateral and will remain in females
- mesonephric ducts (wolffian ducts) are more medial and will remain in males
10
Q
What do the mesonephric ducts do in the foetus and what happens to them?
A
- they drain urine from the mesonephric kidney (2nd kidney)
- in males, testosterone causes these ducts to form the ductus deferens, ejaculatory duct and part of the epididymis
- in females, there is no testosterone made by the ovaries so the mesonephric ducts regress and form non-functional remnants
11
Q
Describe the paramesonephric ducts and what happens to them:
A
- only remain in females as in males the sertoli cells make AMH = the development of these ducts is switched off and they degenerate
- have funnel shaped ends that open into the peritoneal cavity
- migrate caudally to pelvic region and approach in midline and fuse
- upper unfused parts form uterine tubes
- lower fused part forms uterovaginal primordium (will become uterus and vagina)
12
Q
What cellular movements occur in the formation of the indifferent gonad?
A
- at week 5, gonads are indifferent and initially appear as pair of longitudinal ridges made from mesoderm called UROGENITAL RIDGES
- primordial germ cells from the yolk sac move to the genital ridge and form primitive gonads
- primordial germ cells must arrive by week 6 or else the ridges will not develop any further
- the primordial germ cells then form cord-like structures called primitive sex cords
13
Q
How does the testes develop from the indifferent gonad?
A
- the Y chromosome of male has SRY (sex-determining region of the Y chromosome) and this is the testes determining factor
- causes sex cords to become horse-shoe shaped and split into somatic and germ cells
- sex cords break up forming seminiferous tubules
- tunica albuginea forms around each testes and separates cords from the epithelium giving structure
- tubules in testes are solid until puberty when sperm production begins
14
Q
What do leydig cells produce?
A
Testosterone
15
Q
What do sertoli cells produce?
A
AMH (anti-mullerian hormone)
16
Q
What is the pathway of seminiferous tubules to form the ductus deferens?
A
Seminiferous tubules Retes testes Efferent ductules Epididymis Ductus deferens
17
Q
How does the ovary develop from the indifferent gonad?
A
- females have no SRY and so no testosterone production
- other active signals are involved in female development (WNT4 = ovary determining gene)
- primordial germ cells undergo mitosis forming oogonia pool
- oogonia start meiosis but are then in meiotic arrest at month 4 of gestation and are called oocytes
- oocytes associate with follicular cells forming primordial follicles
18
Q
How does the external genitalia of the foetus develop?
A
- cloaca and its membrane thickens forming a pair of cloacal folds
- cloacal folds join cranially forming genital tubercle but are divided caudally
- from the cloacal folds, urethral folds form anteriorly (called labia minora in F) and anal folds form posteriorly
- on either side of the urethral folds there are genital swellings
- genital swellings become scrotal swellings in males and labia majora in females
19
Q
When does the external genitalia start to develop?
A
3 weeks after fertilisation
20
Q
Where does the urethra form from?
A
The middle part of the urogenital sinus
21
Q
How does the penis form?
A
Foetal testes produces androgens which cause the genital tubercle to elongate into phallus
22
Q
What is the end part of the male urethra formed from (the external urethral meatus)?
A
Surface ectoderm
23
Q
How do the bulbourethral glands form?
A
Bulbourethral glands: as outgrowths from penile urethra
24
Q
How does the prostate form?
A
Prostate: as an outgrowth from prostatic urethra
25
How does the vagina form?
Upper part of vagina forms from fused mullerian ducts, lower part from two sinovaginal bulbs which are outgrowths from the urogenital sinus and fuse forming the vaginal plate (becomes a cavity)
26
What physical deformations can occur in female development?
- bicornuate uterus (double uterus due to failure of fusion)
- vaginal atresia (vaginal canal doesn't form properly = block of solid tissue)
- absent uterus and vagina = failure of sinovaginal bulb formation and no uterus)
(the uterus is needed for inducing sinovaginal bulb formation)
27
What is Kleinfelter's syndrome?
Males with XXY
- infertility
- gynaecomastia
- impaired sexual maturation
- leydig cells don't make enough testosterone so low sperm count
28
What is androgen insufficiency syndrome/testicular feminising syndrome?
- male with internal testes and female phenotype
- testes make testosterone but a mutation on the X chromosome causes androgen receptor deficiency
- the testosterone cannot act on receptors so female looking genitalia
29
What is 5-alpha reductase deficiency?
- lack of 5-alpha reductase enzyme which converts testosterone -> DHT
- DHT needed for masculinisation of external male genitalia
- males have enlarged clitoris and internal testes
- at puberty they get hormone surge and grow penis
30
What is Turner's syndrome?
XO
- failure of gonad development as the primordial germ cells degenerate once they reach the urogenital ridge
- there is mesonephric duct regression
- no proper gonads but a 'streak gonad'
- features include webbed fingers and webbed low-set neck
31
How are steroid hormones synthesised and what type of receptor do they bind to?
From enzymatic modification of cholesterol
| Nuclear receptor
32
How are oestrogens formed?
- two main oestrogens are oestrone and oestradiol
- oestrone forms from ovaries direct OR from conversion of androstenedione
- oestradiol forms from granulosa cells OR is converted from oestrone
Cholesterol -> pregnenolone -> progesterone ->
androstenedione ----> testosterone
I I (aromatase)
I I
v -------------------------> v
oestrone oestradiol
33
How are androgens produced?
- adrenal cortex makes ~50% and ovaries make some
- in females, testosterone gets converted to oestrogen, so it is essential we make other androgens
- androgens are DHEA and androstenedione
See week 5 page 6 lecture revision
34
How are progestogens (progestins) produced?
- from cholesterol -> pregnenolone -> progesterone
35
What are the functions of progestogens?
- endometrial development
- smooth muscle control
- maintaining placenta in pregnancy
- mammary gland development
36
What is the function of FSH?
- initiates recruitment of follicles and follicle growth and development
37
What is the function of LH?
- supports theca cells and the LH surge triggers ovulation
38
What is the function of inhibin?
Is secreted by egg after ovulation and this inhibits FHS secretion providing negative feedback so that no more follicles are triggered to develop at that time
39
What hormone changes occur if an egg is implanted?
The CL does not degenerate and it is supported by hCG that the developing embryo produces until the placenta has developed and can take over
40
How do ovulation testing kits work?
measure LH levels, as when these are at a peak you are about to ovulate
41
Draw the hormone graph of the female ovulation and menstrual cycle:
See Week 5 PBL notes page 3
42
What are the three phases of endometrial changes that occur in the menstrual cycle and when do they occur?
1) mensutration = days 0-7
- shedding of endometrium if no fertilisation occurs
- reduced progesterone causes constriction of spiral arteries and ischaemia
- spiral arteries relax periodically and sudden surge of blood carries away the ischaemic tissue in patches lasting ~1 week
- FSH production returns (as reduced progesterone unblocks production of GnRH) and new follicle can start developing
2) proliferative = days 7-14
- due to increasing oestrogen levels and lasts ~10 days
- stroma of endometrium thickens and becomes richly vascularised
- tubular glands become long and coiled and enlarged
3) secretory = days 14-28
- due to increasing progesterone
- mucous production increases and glands are full of glycogen making hospitable environment for implantation to occur
Other changes:
- increased oestrogen causes squamous vaginal cells to mature and epithelium to thicken, increased cervical vascularity and mucous production (so sperm can swim)
- increased progesterone reduces elasticity of cervix and causes thicker cervical mucous production
43
Give an example of a condition caused by hormone XS:
polycystic ovarian syndrome
44
Give an example of a condition caused by hormone deficiency:
hypogonadism
45
Give an example of a condition caused by hormone hypersensitivity:
hirsutism
46
Give an example of a condition caused by hormone resistance:
testicular feminising syndrome
47
How does polycystic ovarian syndrome occur and how is it treated?
- endocrine abnormality that presents with infertility
- no ovulation, lack of menses, weight gain and hirsutism
- complex hormonal imbalances between FSH and LH
- No negative feedback and continuous oestrogen production leading to increased LH to FSH ration of 2:1
- many follicles develop but not far enough to be ovulated
Simply rebalance the hormones to treat
48
Describe the male axis of hormone control between hypothalamus and AP and testes:
Hypo releases GnRH
AP releases LH and FSH
LH triggers leydig cells to produce testosterone
FSH triggers sertoli cells to release AMH causing regression of mullerian ducts, and also produces inhibin which decreases FSH secretion and inhibits
49
What is an endocrine disruptor and describe 4 ways in which they can be classified:
- an exogenous substance that disrupts normal endocrine function
- can increase/decrease hormone production
- can affect the hormone or its receptor
1) Natural hormones (e.g. in fertiliser)
2) Natural chemicals (e.g. in plants)
3) Synthetically produced pharmaceuticals (e.g. contraceptive pill)
4) Man-made chemicals (e.g. DDT pesticides, plastic additives)
50
What three ways do endocrine disruptors function?
1) act as agonists
2) act as antagonists
3) interfere with metabolic processes in the body
51
What reproductive issues can endocrine disruptors cause?
- reduced fertility
- foetal developmental abnormalities
- menstrual problems
- early puberty
- cancers
52
What are phthalates and why are they dangerous?
- man made used in PVC plastic production, found in tablet coatings, insect repellents, solvents
- pose risk to unborn and can cause TDS
53
What are anabolic steroids and why are they dangerous?
- synthetic androgens used to improve athletic function
- have mild testosterone effects and can cause development of secondary sex characteristics
- in large concentrations, trigger negative feedback and testicular atrophy and sterility
54
What are phytoestrogens and why are they dangerous?
- naturally occurring in plants and have mild oestrogen like effects e.g. genistein
- affect on humans is unknown but reduce male fertility in animal studies
55
What is DES and why is it dangerous?
- diethylstilbestrol
- a synthetic oestrogen prescribed to women in 1940-70's that was a miracle drug that prevented early miscarriage but their daughters had repro and fertility issues when they became child-bearing age
56
What is the definition of menopause?
Last menstrual period
The climacteric stage in life when a woman gradually loses ovarian activity due to decreased number of primordial follicles
57
How do you diagnose menopause?
Retrospectively, you cannot diagnose until 12 months after the LMP
58
What is the average age of menopause in the UK?
| What is the age of premature menopause?
52 years
| Earlier than 45 years
59
What are the stages in the development of a pre-ovulatory follicle?
```
primordial follicle
early pre-antral follicle
late pre-antral follicle
antral follicle
pre-ovulatory follicle
```
60
Describe the production of oestrogen in the follicle:
- LH causes theca interna cells to make testosterone
- FSH causes granulosa cells to make aromatase enzyme
- aromatase enzyme converts testosterone into oestrogen
61
What is the pathophysiology of the menopause?
- there are a critical number of good quality follicles left
- there is increased resistance to pituitary hormones (FSH and LH)
- oestrogen levels decrease (as there are less primordial follicles developing)
- progesterone levels decrease as less follicles/eggs get ovulated, so there are less CL to make progesterone
62
What are interventions that can cause non-natural menopause?
- surgical removal of ovaries
- radio/chemotherapy
- smoking
- genetics (Turner's syndrome)
- Hysterectomy with conservation of ovaries MAY cause menopause
63
What are symptoms of the menopause:
- hot slushes, sweaty
- irritable
- anxious
- poor memory
- headaches
- sleep disturbance
- vaginal dryness/bleeding/discomfort
- urinary tract atrophy and UTI's
- CVD risk increases as levels of HDL decrease and LDL increase after the menopause
- osteoporosis (as there are more OC than OB)
- pelvic floor changes and uterus prolapse
64
Describe clinical management of menopause:
1) symptomatic relief - creams, lub, weight loss, stop smoking, bisphosphonates
2) HRT
- contain oestrogen (to alleviate menopause symptoms, usually oestradiol) and progesterone (to protect endometrium)
- various preparations:
1 - oral
2 - transdermal
3 - vaginal (but only treats urogenital symptoms)
4 - IUD with progesterone = HRT and contraceptive BUT patients still need oestrogen
3) non-hormonal treatments:
- clonidine (alpha 2 antagonist to lower BP and stop hot flushes)
- SSRI (selective serotonin re-uptake inhibitor)
- gabapentin (also an anticonvulsant)
65
What are the contraindications of HRT?
- small increased breast cancer risk
66
What type of epithelium lines the vagina?
- non-keratinised stratified squamous
67
What is the pH of vaginal mucous?
- has acidic pH to retard microbial growth (pH 3-4)
68
Where is vaginal mucous produced?
- in the cervix
69
What is the spermatic cord and what are its contents?
- collection of vessels running from testes to the body, suspending the testes in the scrotum
- passes through inguinal canal, entering at deep ring and leaving at superficial ring
- contains:
- >cremasteric muscle
- > DD, lymphatic vessels
- > sympathetic nerves
- > testicular artery
- > DD artery
- > pampiniform plexus of veins
70
Describe the anatomy of the sacrum bone:
See p15 or week 5 lecture revision notes
71
How do you anatomically separate the abdominal and pelvic cavities?
Draw imaginary line between sacral promontory and the pubic symphysis joint
72
What three bones make up the acetabulum?
- ileum
- pubus (anterior)
- ischium bone (posterior)
73
What type of epithelium lines the urethra?
transitional (same as bladder) to allow it to distend and change shape
74
Describe the anatomy of the ovaries:
- 3cm in young, shrink with age, scarred with menstruation
BLOOD SUPPLY:
- ovarian arteries: arise from aorta at level of renal arteries
- ovarian veins (RHS drains into IVC, LHS drains into renal vein)
- drained by aortic lymph nodes
75
Describe the anatomy of the uterus:
- lined by pseudostratified ciliated columnar epithelium
- 4 parts: fundus, body, isthmus, cervix
BLOOD SUPPLY:
- uterine artery - branch of internal iliac artery
- uterine vein - branch of internal iliac vein
- para-aortic lymph nodes drain body
- internal iliac lymph nodes drain cervix
7-8cm long
5cm wide
2.5cm thick
76
Describe the anatomy of the uterine tubes:
- lined by ciliated columnar epithelium
- around 13cm long and found in the free margin of the broad ligament
- 4 parts: infundibulum (with fimbriae), ampulla (wodest part for fertilisation), isthmus and interstitial part
- egg released from one ovary can enter the other
- risk of infection from peritoneum entering
77
What is the rectouterine pouch?
Space between rectum and uterus
78
What is the uterovesicle pouch?
Space between uterus and bladder
79
What is endometriosis?
Where tissue that behaves like endometrium is found outside the womb
- is a chronic condition that can cause painful sex, heavy periods, abdominal pain
80
Describe the main ligaments found in the female reproductive tract:
- broad ligament = peritoneal covering of female reproductive tract
- ovarian ligament = connects ovary to uterus
- mesovarium = shelf of broad ligament that ovaries sit on
- round ligament = remnant of embryonic gubernaculum, connects uterine horns to labia majora
- suspensory ligament = connects ovary to lateral wall of pelvic cavity
81
What is anteversion?
uterus at 90 degrees to vagina
82
What is anteflexion?
anterior bending of uterus on cervix
83
What is retroflexion and retroversion?
Bending in the opposite direction to anteF/V
| In 20% females and has no physiological affect
84
Describe the histology of the uterus and its relevance to periods:
- has myometrium (muscle layer) and endometrium
- endometrium has stratum basalis and stratum functionalis
- stratum functionalis can be divided into compactum (contains gland bodies) and spongiosum (gland necks)
- branches of uterine arteries form straight arteries through the myometrium and into the endometrium forming a plexus in the stratum basalis
- arteries then spiral through the functionalis layer
- in menstruation, the functionalis layer and spiral arteries are lost
- the straight arteries remain and spiral arteries regrow from them
85
Describe oogenesis:
- females are born with all the eggs they will every have in their lifetime
- from fertilisation to 7 months oogonia undergo MITOSIS forming 2-4 million oogonia
- at 7 months MITOSIS stops and meiosis 1 begins when the foetus is still in the womb to form primary oocytes
- the primary oocytes are stuck in metaphase of meiosis 1 until puberty
- once at puberty primary oocyte that has been stuck in metaphase then completes MEIOSIS 1 and forms a secondary oocyte + polar body that degenerates
- the secondary oocyte is then stuck in prophase of MEIOSIS 2
- each month secondary oocyte is released into uterine tube
- secondary oocyte fuses with sperm and both sperm nucleus and egg nucleus are in the secondary oocytes
- secondary oocyte then completes MEIOSIS 2 and gives off a polar body that dies and nuclei of secondary oocyte and sperm fuse forming zygote
86
What triggers follicle cells to start developing?
Unknown, but may be BMP's (bone morphogenic proteins) produced by the connective tissue around the oocytes
87
Describe follicle development and describe the appearance of each:
primordial follicle = one layer of granulosa cells surrounding the egg
primary follicle = oocyte now surrounded by a glycoprotein coat and more layers of follicular cells
secondary follicle = more layers of granulosa cells
- fluid-filled antrum present
- various specialised layers of the granulosa cells develop:
- > theca interna: has many blood vessels for hormone transport
- > theca externa: has collagen fibres
88
Describe how a 'dominant follicle' is selected:
- secondary follicles develop throughout infancy/childhood/puberty
- at start of each menstrual cycle, 10-15 secondary follicles start developing and increase in size
- one week into menstrual cycle, the 'dominant follicle' is selected and the rest undergo atresia
- granulosa cells develop and form a mound called cumulus oophorus that projects into antrum
- after meiosis 1, oocyte and cumulus oophorus separate from follicle wall and float free in antral fluid
- at day 14, thin wall connecting follicle to the ovary wall is digested by enzymes and free follicle carried away by antral fluid to ovary surface
- once follicle is mature it releases its antral fluid and oocyte and the remaining part of the follicle collapses forming corpus luteum
- if no fertilisation occurs, corpus luteum degenerates Z day 10 and undergoes apoptosis forming corpus albicans
89
What is the function of the cumulus oophorus cells?
- protect the oocyte
- surround the oocyte in the follicle and after ovulation
- provide energy for meoisis
90
What happens to the CL if no fertilisation occurs?
- degenerates ~ day 10 and undergoes aptosis forming the corpus albicans
91
Describe what happens in the follicular phase of the menstrual cycle:
- GnRH released from hypothalamus
- AP releases FSH/LH which travel in blood to the ovaries
- FSH causes follicle maturation
- as follicle matures it makes oestrogen
- low oestrogen concentrations inhibit LH release and continue FSH release
- as oestrogen concentration gets higher FSH release is inhibited and LH release allowed
- at day 10 high oestrogen causes large LH surge
- oocyte ovulated at day 14 and remaining follicle forms CL
- CL releases progesterone and inhibin
92
Describe what happens in the luteal phase of the menstrual cycle:
- as CL develops its production of inhibin increases
- high inhibin levels stop FSH release as it is no longer needed
- high progesterone levels affect the hypothalamus and stop GnRH release
- less GnRH = less FSH/LH
- as follicle undergoes atrophy (as it is not fertilised) oestrogen and progesterone levels decrease
- GnRH production is no longer inhibited and new menstrual cycle can occur
93
When should you do blood test for progesterone levels?
~day 21 of cycle as this is when they peak
94
What is the mechanism of action of the combined contraceptive pill?
- contains progesterone and oestrogen
- progesterone -> thickens mucous at womb entrance so sperm cannot enter, thins uterus lining making implantation difficult
- oestrogen -> stops production of FHS/LH so follicles do not develop into an egg that can be ovulated
- pills can be monophasic (same hormone concentration daily) or phasic (mimic hormone levels throughout the menstrual cycle)
- have 7 day break to allow menstruation to occur
95
What is the mechanism of action of the uncombined (mini) contraceptive pill?
- progesterone only -> thickens mucous at womb entrance so sperm cannot enter and thins uterus lining making implantation difficult
a) type 1 - 3hr pill, must be taken within 3hrs of the same time each day
b) type 2 - 12hr pill, must be taken within 12hrs of the same time each day
- with type 2 pill an egg is NOT released in 97/100 cycles, as the progesterone levels are high and signal to the hypothalamus to stop GnRH release so no FHS/LH are produced and no egg develops and ovulates
96
What is infertility?
Failure of couple to conceive a child after one year of unprotected sex
97
What are causes of infertility in males and what percentages of infertility cases are accounted for by these causes?
- 30-40 %
- untreated hypogonadism of any cause (systemic illness, under-weight, hypopituitarism)
- testicular disease (DD blocked and low sperm count)
- ejaculatory dysfunction (congenital/prostatic infection)
- retrograde ejaculation (semen re-directed into urinary bladder as upper urinary sphincter doesn't close at right time)
- Kartagener's syndrome (immobile sperm)
98
How do you assess males for infertility?
- semen analysis
- testicular biopsy
- alcohol/drugs
- undescended testes
- testicular damage
99
What are causes of infertility in females and what percentages of infertility cases are accounted for by these causes?
- 20% cases
- any cause of amennhorea (0ver-exercising, low fat diet, stress, anorexia)
- any cause of oligomenorrhoea (35 days without menstrual period associated with sub-optimal ovulation/anovulation)
- polycystic ovarian disease
- post-pill amenorrhoea
- hypopituitarism
- absent uterus/lack of endometrium (congenital)
100
How do you assess females for infertility?
- period regularity
- vaginal examination to check uterus/ovaries
- serum progesterone
- hysteroscopy (using hysteroscope - like a narrow telescope with a light and a camera - to examine inside the uterus)
