Endo/Repro 2 Flashcards
Ovary structure
Medulla inside - blood vessels and nerves
Cortex outside - follicles embedded in stroma
Follicles around outside, various stages before follicle ruptures and releases egg, forms corpus luteum
Development of primary oocytes
Primordial germ cells
- present at 4-8 weeks gestation
- 600,000 present
->
Oogonia
- at 6-30 weeks gestation
- 7,000,000 present
->
Primary oocytes
- present at 10 weeks gestation to 45 years olf
- 2,000,000 present
-> remain arrested in prophase I of meiosis I, stay here in dormant state for many years
(primary oocyte with layer of granulosa cells = primordial follicle)
Folliculogenesis
Primordial
— spontaneous process, slow, at any age —
Primary (pre-antral)
— requires FSH and LH so only after puberty, rapid growth —
Secondary (antral)
— LH surge, only one will dominate here —
Tertiary (fully mature, will be released in ovulation)
- primary oocyte resumes meiosis, increase volume follicular fluid, stigma formed
Process happens across MULTIPLE menstrual cycles, not just one
Primordial follicles
Primary oocyte surrounded by single layer of flattened granulosa cells (derived from stroma)
Form pool around around edge of cortex
Follicular atresia
Most follicles will die, programmed cell death
- occurs at all stages, but mainly in primordial and primary follicle stages
- much occurs before birth and throughout childhood, only 500,000 follicles remain at puberty
- not altered by pregnancy or contraceptive pill
- accelerated by genetic disorders and chemotherapy
Primary follicles
Increased size oocyte
Proliferation of granulosa cells
Zona pellucida (essential outer rim, what sperm will bind to) formed
Theca interna formed
Secondary follicles
Fluid-filled antrum
Formation requires LH and FSH
Approximately 12 form at the start of each menstrual cycle - most will still undergo atresia
Produce oestradiol
Formed by
- further proliferation of granulosa cells
- formation of antrum
- activation of theca interna
Two cell-two gonadotrophin theory for ovarian steroidogenesis
LH -> in theca cells (outside follicle)
- convert cholesterol to testosterone
FSH -> in granulosa cells (surrounding oocyte)
- convert testosterone - from theca cells - to oestrogen by aromatisation
Therefore, without FSH, androgen secretion predominates
Follicular selection
Dominant (to be ovulated) follicle selected around day 9 of cycle
- produces 90%+ of oestradiol coming from ovary, as well as inhibin A (to feedback and regulate FSH)
May be due to:
- high oestradiol:testosterone levels in follicular fluid
- high aromatase activity
- favoured blood supply
- optimal exposure to growth factors
- more FSH receptors
(declining FSH will now kill off other follicles)
Tertiary follicle
Oocyte at side of follicle
Cumulus oophorous is stalk of granulosa keeping oocyte attached to follicle wall
Massive antrum - hormone packed fluid
ONLY ONE EACH CYCLE
Formation requires LH surge
- brief further proliferation of granulosa cells
- leutinisation of granulosa cells (so now favour progesterone)
- swelling of follicle
- formation of stigma (site of rupture) - will rupture 24h after LH surge onset, empty follicle forms corpus luteum
- resumption of meiosis - to meiosis II where it stops until after fertilisation
Female reproductive tract
- fertilisation happens in the ampulla
- implantation happens in the uterus
Myometrium (smooth muscle layer) and endometrium (inner mucosal layer)
Endometrium - regulated by ovarian hormones, varies in thickness by cycle
Purpose of menstrual cycles
- controlled development of follicles at correct time
- for release of oocytes when fertilisation likely
- preparation for implantation
- allows next cycle to start ASAP in absence of fertilisation
It is energetically expensive to continually build up and break down endometrium, so must be necessary!
Menstrual cycle phases
Day 1-13 - pre-ovulatory phase
- proliferative, endometrium growing
- driven by oestrogen
- > vasoconstrictive, angiogenesis, coiled blood vessels lengthen
Day 14 - ovulation
- hormone changes for maximal endometrial thickness
Day 15-28 - post-ovulatory (luteal) phase
- driven by progesterone and oestrogen
- progesterone released from corpus luteum (lingers for 14 days unless pregnancy) to maintain secretory lining - PRO GESTATION
- blood vessels constrict and recoil (shut off at base, spasm)
Day 1-5 - menses (mesntrual phase)
- lining breaks down, bleeding
Menstrual cycle features
- cyclic endocrine and physiological changes associated with folliculogenesis
- first cycle is menarche (puberty), last is menopause (typically age 51)
- mean length is 28 days
Early follicular phase
= menstrual phase
Day 1-5
FSH elevated
LH basal
Oestradiol low
Inhibin low
Progesterone low
10-20 secondary follicles growing
Menstruation
Late follicular phase
Day 1-13
FSH falling
LH rising
Oestradiol rising - positive feedback now, so levels rise and provide cue for LH surge
- dominant, so repair of vessels by angiogenesis and vasoconstriction
Inhibin rising
Progesterone low
Selection of dominant follicle at day 7-8
Endometrium repairing
Ovulatory phase
Day 14
LH surge
Oestradiol temporary fall
Inhibin temporary fall
Progesterone rising
Ovulation of tertiary follicle
(basal temperature increase)
Luteal phase
Day 15-28
FSH low
LH low
Oestradiol high
Inhibin high
Progesterone high
Corpus luteum present
Endometrium in secretory state
Leutolysis after 14 days (unless conception)
Hypothalamo-pituitary-ovarian axis
Hypothalamus arcuate nucleus
-> GnRH (release every 90 mins in day 1-14)
Anterior pituitary
-> LH + FSH
Ovary
-> oestradiol (+ve and -ve feedback to pituitary and hypothalamus), inhibin (-ve feedback to pituitary), progesterone (-ve feedback to hypothalamus)
LH surge
Gradual onset
Lasts 48 hours
- leutinises the dominant follicle (oestrogen declines, progesterone rises)
- wakes up oocyte from dormant meitotic stage
- follicle releases egg
Ovulation occurs 12-24 hours after LH peak
(also involves FSH)
Feedback effects of oestradiol
Low levels
- > negative feedback
- rapid onset, stronger on FSH than LH
High levels (for more than 48h)
- > positive feedback
- slow onset, stronger on LH than FSH
Feedback effects of inhibin
Main source of negative feedback on FSH
Acts at pituitary
Release follows pattern of oestradiol
Feedback effects of progesterone
High levels
- > negative feedback to hypothalamus
- > block oestradiol positive feedback
Hypothyroidism + menstruation
Annovulation + irregular/absent periods
Low oestrogen status
Raised TRH - potent stimulator of prolactin Raised prolactin Lowered GnRH Lowered FSH Lowered oestradiol
Polycystic ovarian syndrome + menstruation
Annovulation + irregular/absent periods
High oestrogen status
Raised androgen
Raised LH in constant state, no pulsatile activity
No progesterone release (no menstruation, still lots of endometrial growth so high risk endometrial cancer)
Lowered FSH
Raised oestradiol
(also theory that increased sympathetic nerve activity is driver)
(as many follicles in ovaries, all producing small amounts of oestrogen, so endometrium grows)
Treatments of ovulatory dysfunction in PCOS
Clomiphene citrate - anti-oestrogen to encourage more FSH, induces ovulation
Metformin - type II diabetes common, and need to suppress insulin drive to ovaries (drives theca cell androgen secretion)
hMG, FSH - forms of FSH, aid in conception
Ovarian diathermy - surgery, to burn core of ovary that is producing androgens, suppress LH stimulation, restore normal circulation of hormones
(needs repeating every 6-9 months)
Myo-inositol - for insulin resistance
Gender differentiation in embryo
Early on, all have both mesonephric (Wolffian) and paramesonephric (Mullerian) ducts
- so potential to be male or female
Primordial germ cells migrate from yolk sac
- to invade gonad
- drawn by chemoattractants released by genital ridge (chemokine CXCL12)
- – programmed to die if don’t reach genital ridge (if left elsewhere in body -> teratocarcinoma) —
- trigger proliferation of genital ridge
- make primitive sex chords (nurture and wrap around germ cells)
Embryonic differentiation to female
ABSENCE OF SRY/TDF GENE
Germ cells form ovaries
Primitive sex chords become follicular cells
No androgens present
Wolffian duct regresses
Mullerian duct becomes fallopian tube, uterus, vagina
Urogenital sinus remains open
Vestibule and labia minora form
Genital tubercle small, becomes clitoris
Genital swellings don’t close, become labia majora
Gubernaculum cord pulls ovaries down from pelvis (slightly)
- retain Gartner’s duct, male remnant
Embryonic differentiation to male
PRESENCE OF SRY/TDF GENE
Germ cells form testes
Primitive sex chords become seminiferous tubules
Androgens present
Wolffian duct becomes epididymis, vas deferens, seminal vesicle, ejaculatory duct
Mullerian duct regresses
Urogenital sinus closes - essential for proper growth
Urethra and prostate form
Genital tubercle large, becomes penis
Genital swellings close, become scrotum
Gubernaculum cord in scrotum pulls testes down from pelvis
(as testes grow, sertolli cells produce anti-Mullerian hormone to kill off Mullerian duct)
- retain utricle in prostate, blind ended tube, remnant of Mullerian duct
Embryonic development of uterus
Two Mullerian ducts fuse in midline
-> form utero-vaginal canal, will be uterus and top 1/3 of vagina
Lower 2/3 of vagina formed from resorbed wall of urogenital sinus, gives separate entrance to vagina (with hymen over the top)
Fusion can go wrong, cause difficulties getting pregnant, miscarriages
- atresia at level of cervix, uterus septus duplex, double vagina
Developmental abnormalities in gender differentiation
Turner’s syndrome
- XO
- two ovaries needed for normal ovarian development
- so no puberty, no formation of secondary sex characteristics
Androgen insensitivity syndrome (testicular feminisation)
- XY, but mutation in testosterone receptor
- grow female reproductive tract, but with testes (need to be removed, cancer risk) no ovaries so infertile
Penis at 12
- tribe, where XY children are born phenotypically female
- mutation in enzyme converting testosterone to more potent dihydrotestosterone (DHT), so not enough in foetus to trigger male differentiation
- testosterone surge in puberty, so triggers change to male phenotype
(penis grows, facial hair, voice break etc)
Endometrium
Mucosal lining of uterus Simple columnar epithelia and stroma Basal and functional layers Simple tubular glands Straight and spiral arteries
Function:
- sperm transport
- hatching of fertilised egg
- nourishment of blastocyst
- surface for blastocyst implantation
Endometrial changes in menstrual cycle
PROLIFERATIVE - day 6-14 - initially 2mm thick (no surface epithelia or functional layer) - thickens to 4mm - glands increase in length - spiral arteries uncoil (influenced by oestradiol)
LUTEAL - day 14-28 - glands lengthen and distend - stroma oedomatous, 6-7mm thick - decidual cells appear (influenced by progesterone)
MENSTRUAL - day 1-5
- endometrium loses water and shrinks
- spiral arteries coil and constrict
- upper functional layer becomes ischaemic, dies
- spiral arteries dilate, bleeding
- increased contractions of uterus - prostaglandins
(fall of progesterone and oestrogen)
Breakthrough vs withdrawal bleeding
BREAKTHROUGH
- continuous steroid support (oestradiol or progesterone), eg from combined pill or PCOS
- endometrium over-developed, heavily vascularised, fragile
- repetitive bleeds occur in different parts of endometrium
- bleeding unpredictable, may be excessive
WITHDRAWAL
- loss of steroid support eg in period, progesterone only pill
- if no endometrium, no bleed
Primary amenorrhoea causes
Failure of menses to occur by age 16
Mainly hypogonadism:
- hypogonadotrophic - congenital (hypopituitarism), endocrine (cushings), tumour, systemic illness, eating disorder. No LH or FSH.
- hypergonadotrophic - abnormal sex chromosomes (XO Turner’s), normal sex chromosomes (XX/XY). Excess FSH and LH in an attempt to drive non-functioning ovaries.
Eugonadism:
- anatomical, intersex, inappropriate feedback
Secondary amenorrhoea causes
Cessation of menses after menarche
- pregnancy, ovarian disorders, pituitary/hypothalamic disorders, functional (eg in stress, shut-down of GnRH pulse)
Menorrhagia
Excess blood loss, interfering with quality of life
- number of days of bleeding decreases with age
- blood loss increases with age
- cycle length reduces with age
Caused by:
- bleeding disorders
- structural risk factors - uterine fibroids, endometrial polyps, endometriosis, endometrial hyperplasia, endometrial cancer
Treatment of menorrhagia
Medical:
- mefenamic acid (NSAID)
- tranexamic acid (anti-fibrinolytic)
- cyclical progesterone (the pill)
- mirena (IUD coil that releases progesterone, absorbed locally)
- GnRH analogues
Surgical:
- endometrial ablation (local anaesthetic block done as outpatient, fry away basal layer endometrium so won’t grow back)
- polypectomy
- fibroid embolisation
- myomectomy
- hysterectomy
Oligomenorrhoea and polymenorrhea
OLIGO
Infrequent periods, cycles lasting more than 35 days
POLY
Over-frequent periods, cycles lasting less than 21 days
(50% age-related, 50% pathological)
- always needs to be investigated, could be endometrial cancer
Polycystic ovarian syndrome (PCOS)
Need 2/3 of:
- oligomenorrhoea or amenorrhoea
- hyperandrogenism (clinical or biochemical, high LH:FSH ratio)
- polycystic ovaries on ultrasound - 12 or more follicles in at least 1 ovary measuring a certain size
Affects 1/5 women
Due to hyperinsulinaemia, genetics, racial differences (fat/thin PCOS?)
Dysmenorrhoea
Painful menstruation
1/10 interferes with daily activity
Common in teenagers and early 20s
Related to prostaglandins?
Secondary to - endometriosis, pelvic inflammatory disease, copper coil
Endometriosis
Ectopic endometrial tissue - lining of uterus grows outside of uterus, on umbilicus, rectum, outside uterus, ovaries, bladder
Cyclic development, pelvic pain
-> infertility
Structure of cervix
Connective tissue, lined by endocervix
Secretory epithelium
Tubular glands, open into crypts (cervical clefts)
Filled with mucus made of mucopolysaccharide
-> barrier to infection and sperm
Cervical secretions increase at ovulation, and water content increases
(driven by oestradiol, reversed by progesterone)
Premenstrual syndrome
5% experience severe PMS
Regularly reoccurring symptoms in luteal phase of each menstrual cycle
- irritability
- anxiety, depression
- loss of confidence
- mastalgia (breast pain) - increased blood flow, oedema - driven by steroids
- bloating - due to progesterone usually antagonises aldosterone - weight gain, oedema of limbs
Unknown cause
Causes of premature ovarian failure
When younger than 40yo:
Idiopathic Gonadal dysgenesis - Turner's syndrome XO, Perrault's syndrome, 47XXY Autoimmune Genetic associations Infarction Iatrogenic
Menopause features, and hormone activity
- reproductive decline for 5-10 years leading up to - become onovulatory or have incomplete cycles
- 6 months after cessation of cycles, ‘post-menopausal’
- average age 53 (has not changed as life-expectancy increases)
FSH massive rise (diagnostic)
LH rise
Progesterone fall (now mainly coming from adrenals not ovaries)
Oestradiol fall (now mainly from peripheral conversion from androgens, mainly androstenedione)
Testosterone continues (ovaries and adrenals)
Symptoms of menopause
Mostly from oestrogen withdrawal:
- genital atrophy of reproductive tract
- hot flushes
- sweating
- joint and muscle pain
- skin atrophy (drier, more wrinkles)
- memory and concentration reduced
- oesteoporosis
- cardiovascular changes
Due to ageing:
- insomnia
- dizziness
- palpitations
- shortness of breath
- weight changes
Atrophic changes in genital tract following menopause
- reduced menstrual flow, longer intervals, then cessation
- uterus reduces size
- cervical glands stop producing mucus
- skin overlying genitalia becomes thin and pale
- genitalia shrink
- vaginal mucosa becomes thinner, pH increases
- urethral mucosa becomes thinner
- pelvic floor weakens
Treatment of main symptoms menopause
HOT FLUSHES
- relaxation techniques
- plant oestrogens
- placebo
- HRT
- SSRI
- lifestyle changes (dress in layers, stop smoking, lose weight)
OSTEOPOROSIS
- HRT - reduce bone breakdown (use esp in premature menopause)
- Bisphosphonates - reduce bone breakdown
- SERMs (selective oestrogen receptor modulators) - reduce bone breakdown
- parathryoid hormone - rebuild bone
Osteoporosis and the menopause
Oestrogens stop bone loss:
- stimulating osteoblast cells
- promote production of local growth factors
- increase calcitonin output
- enhance calcium absorption from diet
Risk also increased by:
- family history, sedentary lifestyle, low BMI, smoking, alcohol, steroid use, hyperthyroidism/hyperparathyroidism
Oestrogen effects on cardiovascular disease
CVS protection:
- increase HDL in blood - favour transport of cholesterol to liver for breakdown
- LDLs favour transport of cholesterol to other organs
CVS harm:
- alters clotting factors, to increase risk of thromboembolism
(need to watch in pregnancy or on pill)
Hormone replacement therapy
Cyclic combined - continuous oestrogen, 12 days progesterone also
Continuous combined - continuous oestrogen and progesterone
Oestrogen only - only if have had hysterectomy and no endometriosis (need progesterone to protect against endometrial cancer)
Given orally, patches, vaginal ring
Benefits - symptoms menopause alleviated, protect against osteoporosis
Risks - thromboembolism, breast cancer, endometrial cancer, ovarian cancer
(so avoid giving for more than 5 years)
Male menopause?
Increased frequency of erectile dysfunction as age
- 1% men experience:
- decreased frequency morning erection
- decreased frequency sexual thoughts
- erectile dysfunction to low testosterone levels
(only tends to be a problem well after the average age of female menopause)
Sperm transport
15cm journey from upper vagina to ampulla of oviduct
Takes 5mins-7days (majority 3-5hours)
Active swimming and passive transport - via cervical mucus and uterine contractions
VAGINA
Initially held in coagulated semen, then liquefies in 15 mins -> surge of motility
Active swim into cervical mucus
Low pH kills sperm within 20-30 mins
CERVIX
(barrier - 1/1000 get through)
Can only be penetrated between days 9-16 of cycle due to density of mucus (fern pattern needed)
Needs active swimming at 1cm/min
Either traverse 2cm canal in 6-8mins, or rest in cervical crypts for up to 24hours
UTERUS
Swim in uterine fluid
Moved by active swimming, and uterine contractions (only myometrium, not whole uterus as in contractions)
OVIDUCT
Only 40,000 enter
Utero-tubal junction opens intermittently
Oviductal fluid stimulates sperm motility, cilia propel along -> flow to carry sperm along
400 get near egg in ampulla
Oocyte transport
PICKUP
- oocyte surrounded by sticky cumulus oophorous, adheres to surface of ovary after ovulation
- fimbriae extend (high blood flow at progesterone peak)
- fimbriae sweep over ovary, sweep egg into oviduct by cilia
TRANSPORT
- rapid through ampulla, then tube locking at ampullary-isthmic junction (2-3 days) to allow time for fertilisation
- controlled by changing levels of oestradiol and progesterone
Stages of fertilisation - sperm
CAPACITATION
- takes 4-6 hours, usually in uterus
- leaching, to remove glycoprotein coat and seminal plasma proteins - to make less stable, more permeable to calcium
- now capable of fertilising egg
ACROSOME REACTION
- occurs near egg, after binding to zona pellucida
- triggered by progesterone/zona protein 3
- outer acrosome membrane fuses with plasma membrane, acrosome contents released
PENETRATION OF CUMULUS OOPHORUS
- granulosa cells disperse after release of acrosome contents (hyalurodinase)
PENETRATION OF ZONA PELLUCIDA
- few sperm attach to outer surface of zona by inner acrosome membrane
- attachment activates zona lysin enzyme, burns hole through zona pellucida (at oblique angle)
- only one sperm successfully penetrates
FUSION WITH VITELLINE MEMBRANE
- sperm now in perivitelline space, tail through zona pellucida
- post acrosome membrane and vitelline membrane fuse, sperm sinks into egg
(fusion helped by microvilli on vitelline membrane)
Stages of fertilisation - egg
ZONA REACTION
- entry of sperm -> calcium waves in egg
- calcium causes exocytosis of cortical granules
- granules contain enzymes so no polyspermy
- block of zona lysin enzyme
RESUMPTION OF MEIOSIS
- moves on from metaphase II, recommences meiotic division after sperm enters cytoplasm
FORMATION OF PRONUCLEI
- polar bodies extruded
- male and female pronuclei formed
SYNGAMY AND FIRST CLEAVAGE
- pronuclei fuse
- two groups of chromoses assemble ready for mitotic division
Early embryonic development
30 hours - 2 cell stage
3.5 days - advanced morula (32 cells)
Early blastocyst phase (enters uterine cavity)
5.5 days - implantation begins
Errors of fertilisation
Polyspermy
- two sperm enter egg -> triploid embryo
- due to failure of zona reaction
- no viable foetus, just lump of cystic features (still produces hormones and pregnancy-like features)
- cancer like, can invade blood supply, so needs removal/chemotherapy - recommend no further pregnancy for 6 months
Failure of extrusion of polar body
- second meiotic division is faulty, polar body remains in egg
- > triploid embryo (two chromosomes, one polar body)
- can be compatible with life, but usually severely disabled
Twins
Monochorionic/Dichorionic - one/two placentas
Monoamnionic/Diamnionic - one/two amniotic sacs
DCDA eg in dizygotic twins
Monozygotic:
Can split at various stages, the earlier the better:
- first few days -> DCDA
- next few days -> MCDA (risk of twin-twin transfusion syndrome and entanglement)
- next -> MCMA
If over 12-14 days, foetal fusion (conjoined twins - sometimes not compatible with life depending on location of join)
Hormone test HcG for pregnancy
Beta HcG (human chorionic gonadotrophin) Produced by trophoblasts in placenta Glycoprotein Most sensitive test in first week (often gives false hope)
Maternal changes in early pregnancy
CARDIOVASCULAR
- increased blood volume, plasma volume, red cell mass, cardiac output
- reduced peripheral resistance
RESPIRATORY
- increased minute volume, tidal volume, resp rate, alveolar ventilation
- sensation of breathlessness
- reduced airway resistance, total lung capacity
RENAL
- relaxation of smooth muscle, renal blood flow increases
- increase renal renin (to balance natriuretic effect of progesterone)
- increased GFR
GASTROINTESTINAL
- acid reflux common
- reduced gastric secretions, gastric stasis, reduced intestinal motility
(physiological changes reverse after 6 weeks birth, postpartum period)
Development of placenta
Invasion of endometrium, implantation
Lacunae formed in syncytiotrophoblast
Primary villi formed
Secondary and tertiary villi formed, cytotrophoblastic shell
Branching villi formed
Differentiation of chorion laeve and chorion frondosum
Final structure of placenta
(changes in placental barrier throughout pregnancy, invasion and erosion of spiral arteries)
Implantation
Embryo attaching to uterine wall
Penetrates circulatory system of mother
To form the placenta
Begins 2-3 days after embryo enters uterus
(limited by time and space, narrow window)
Endometrium is prepared for implantation by cytokines, growth factors and lipids - modulated by progesterone - endometrium receptive for only few days
May still get positive pregnancy test before this!
Implantation - attachment phase
Usually on upper posterior wall (if in cervix, interstitial portion or fallopian tube -> ectopic pregnancy)
Zona pellucida needs to dissolve first - degraded by proteolytic enzymes either from trophoectoderm or uterine secretions Involves decidualised endometrial adhesion molecules - integrins and selectins Early blastocyst (~day 5), attaches and grows under endometrium, not in uterine cavity (this will seal, as pregnancy grows in wall)
Attachment limited by serine proteases and metalloproteinase
- plasminogen activators, provide plasmin for degradation of extracellular matrix
Implantation - invasive phase
When endothelial endometrium breaks down, efflux of metabolites
-> taken up by blastocyst, used to feed growth
Balance of restraining and promoting growth factors, cytokines and enzymes:
- plasminogen activation inhibitor (released from decidual cells)
- metalloproteinases
- TGFalpha
- TGFbeta
- > DECIDUAL REACTION - triggered by attachment
- increased vascularity
- oedema
- change in morphology and biochemical makeup of stromal cells to form decidual cells
Decidua basalis is platform for placenta
Progression from implanted embryo (day 9)
Syncitiotrophoblast merges with enlarging blood vessels to form lacunae - essential to keep maternal blood supply separate
Amniotic cavity, ectoderm and endoderm form from inner cell mass
Primitive yolk sac (bit around inner cells mass) will fuse and be obliterated as amniotic sac grows
Villi formation
Primary villi from cytotrophoblast core
- foetal, grow up into blood space
Later develops mesodermal core to form secondary villus
Eventually branching villi into intervillous space, filled by maternal blood from uterine vein
Foetal blood in umbilical artery circulates through
-> Cotyledon, arrangement of anchoring villi within lobe
Eventually placenta will weigh about as much as baby
Function of placenta
First 7 weeks, pregnancy is supported by corpus luteum from ovary
After, by placenta
- organ of respiration
- organ of nutrient transfer and excretion
Syncitiotrophoblast produces protein and steroid hormones (pregnant women can have no pituitary) -> progesterone -> oestrogens -> HcG -> placental lactogen
Progesterone during pregnancy
C21 steroid hormone
Initial rapid rise over first 4 weeks (from corpus luteum)
Plateau 4-10 weeks (placenta begins secretion, CL stops)
Progressive rise 10-40 weeks
Placenta production independent from foetus, never gets to foetal blood stream
(works with oestrogens)
- > maintenance and growth of endometrium
- > growth of uterine myometrium
- > muscle relaxation - myometrium, GI muscles
- > metabolic effects - hyperthermic, appetite
Oestrogens during pregnancy
C18 steroid hormone, eg oestradiol
Slow rise over first 10 weeks, progressive as placenta grows
Maximal at 40 weeks
Requires feto-placental unit (stops in absence of foetus)
(works with progesterone)
- > stimulate endometrial and myometrial growth
- > prepares uterus for labour by increasing contractility and softens cervix
- > alters connective tissue
Placenta’s steroidogenic activity
Can convert cholesterol to progesterone
Can convert testosterone to oestrogen
Cannot convert progesterone to testosterone or oestreogens
DHEA -> testosterone -> oestrogens
- placenta production of oestrogens dependent of foetus
- DHEA from foetus, conversion to oestrogens in placenta
Human chorionic gonadotrophin
hCG
Glycoprotein (not steroid)
Similar structure and action to LH
Early peak 10 weeks
Late peak 30 weeks
- > maintains corpus luteum secretion of oestrogen and progesterone
- > drives steroidogenesis in foetal gonad and adrenal
Human placental lactogen
hPL
Very large polypeptide
Similar structure and actions to GH
Rises progessively with placental growth
- > foetal growth
- > metabolic adjustments - mobilise free fatty acids from maternal stores, reduce maternal utilisation of glucose so can be used for foetus, stimulate insulin secretion and inhibit its effects at peripheral sites, transfer amino acids to foetus
Drugs in placenta
Most drugs/metabolites can cross the placenta
Greatest risk 4-12 weeks
- very safe below 4 weeks, still slight risk after 12 weeks (finished most development, just need to grow and mature)
Rate crossing placenta depends on:
- solubility of ionised molecules in fat
- thickness of trophoblasts
