SUGER Flashcards
Define Genotype
complete genetic composition of an individual
In humans, is the sex of the embryo determined by the sperm or egg?
The spermatozoa - can contribute an X or Y. The egg is always X.
Why does the presence of the Y chromosome lead to the development of the male gonads?
Presence of the SRY gene
(Sex
determine Region of the Y chromosome)
Which protein does the SRY gene on the Y chromosome produce?
Testis determining factor: under its influence male development takes place.
What is the importance of testis determining factor?
Under its influence male development takes place.
If there is an absence of the SRY gene as no Y chromosome what is formed?
female gonads (ovaries)
What is lyonisation?
When two X chromosomes are present (in a female), only one is functional,
the non-functional X chromosome condenses to form a nuclear mass called
the sex chromatin or BARR BODY
From which site do both male and female gonads derive embryologically?
Urogenital ridge
When are embryos no longer indifferent?
They are indifferent until the end of the 6th week.
Describe the migration of primordial germ cells.
Originate in the epiblast and migrate through the primitive streak. They migrate along the dorsal mesentery of the hindgut to reach and invade the genital ridge by the 6th week.
Up until when are the primordial gonads undifferentiated?
6th week
What is the indifferent stage?
When the Wolffian and Müllerian ducts are both present. It is impossible to tell the sex of the embryo.
- undifferentiated reproductive tract double duct system
When do the testes begin to develop?
7th week - SRY gene expressed at this time in the urogenital ridge cells and triggers development
Name the two tracts that most of the reproductive tracts develop from
- Wolffian ducts
- Mullerian ducts
In males which genital duct system persists and which one regresses?
• In the male, the Wolffian ducts persist and the Mullerian ducts REGRESS
Why does the Müllerian duct degenerate in males?
Sertoli cells of the testes produce a protein hormone - Mullerian-inhibiting factor (MIF)
- The SRY gene induces the expression of MIF which in turn results in
the degeneration of the Mullerian duct
What does testosterone stimulate?
Differentiation of the Wolffian duct into the epididymis, vas defrens, ejaculatory ducts and seminal vesicles
Which cells secrete testosterone in embryological development?
interstitial cells of Leydig
When do Leydig cells start producing testosterone?
8 weeks
In females which genital duct system persists and which one regresses?
Mullerian ducts persist and the Wolffian ducts
REGRESS
Why does the Müllerian duct degenerate in Males?
Due to the inhibiting substance being released from Sertoli cells. Sertoli cells release MIF.
In females why does the Mullerian system persist and why does the Wolfian duct regress?
Absence of SRY gene, no testosterone and MIF secreted
- absence of the MIF Mullerian system stays and develops into fallopian tubes and uterus
- absence of testosterone Wolffian duct degenerates
What does the Müllerian duct form in females?
The uterine tubes, uterus, cervix, fallopian tubes and proximal 1/3 of the vagina.
Until what week are male and female primitive gonads identical?
6th week
what can germ cells develop into?
Sperm and Ova, gamete production
Where do germ cells originate from?
• Originate from the yolk sac of the hindgut
What is the first stage of gametogenesis?
the proliferation of the primordial (undifferentiated)
germ cells by MITOSIS
When does mitosis occur in embryonic testes to generate primary spermatocytes?
- some at birth
- mostly begins during male puberty and continues through life
When does mitosis of germ cells occur in the ovary?
- primarily during fetal development resulting in the generation of primary oocytes
What is the second stage of gametogenesis?
meiosis
What is the importance of meiosis in gametogenesis?
It prevents polyploidy and increases genetic variability and so diversity through crossing over and independent assortment
Spermatogenesis: what does meiosis 1 produce?
2 secondary spermatocytes.
What are the start and end products of meiosis in oogenesis?
Start primary oocyte.
Middle: secondary oocyte.
End: 1x ovum.
When is the first polar body produced in oogenesis?
after the first meiotic division - has no function
Spermatogenesis: what does meiosis 2 produce?
4 spermatids.
Describe the timing of the second meiotic division in males
- In males, this occurs continuously AFTER puberty with the
production of spermatids and ultimately mature sperm cells
Describe the timing of the second meiotic division in females
- In females the second meiotic division does not occur until
AFTER FERTILISATION of a secondary oocyte by a sperm -
this results in the production of a zygote (contains 46
chromosomes - 23 from the oocyte (maternal) & 23 from the
sperm (paternal)) & the second polar body which also has no
function
where does meiosis occur in males?
seminiferous tubules
Where does meiosis occur in females?
ovaries
Describe oogenesis.
Oogonia undergo around 30 mitotic divisions in utero. The oogonia develop into primary oocytes and begin a meiotic division by replicating their DNA. They do not complete meiosis 1 in the foetus = meiotic arrest. At puberty, there is renewed activity in the ovaries and those oocytes destined for ovulation complete meiosis 1. Meiosis 2 occurs if the secondary oocyte is fertilised; this will produce one ovum.
How long does spermatogenesis take?
Approximately 60 days.
Why does each primary oocyte yield only one secondary oocyte?
Because only one ovum can be yielded per primary oocyte. The secondary oocyte divides into one ovum and a second polar body.
Where are Detrusor muscles found, innervation and inhibited or stimulated during filling and micturition
- Found on the walls of the bladder, smooth muscle
- Parasympathetic innervation (causes contraction)
- micturition stimulated
- filling inhibited
Describe internal urethral sphincter muscle type, innervation and inhibited or stimulated during filling and micturition
Smooth muscle
Sympathetic (contraction)
Filling - stimulated
micturition - inhibited
Describe external urethral sphincter muscle type, innervation and inhibited or stimulated during filling and micturition
Skeletal muscle
Somatic motor (causes contractions)
Filling - stimulated
micturition - inhibited
What is the role of the external striated urethral sphincter?
contraction of the external striated urethral sphincter can contract and prevent urination even if the detrusor muscles and contracting strongly
Describe bladder filling
- Parasympathetic input to the detrusor muscle is minimal, relaxed
- when the detrusor muscle is relaxed the internal urethral is passively closed
- strong sympathetic input to the internal urethral sphincter
- strong sympathetic input to external urethral sphincter via somatic motor
- means during the filling phase the detrusor muscles are relaxed and the internal and external sphincters are closed
Describe the bladder reflex arc
- Bladder fills with urine, and the bladder walls stretch
- Sensory nerves (afferent) detect the stretch and transmit to the spinal
cord - Interneurones within the cord relay the signal to the parasympathetic
efferents (PELVIC NERVE) - The pelvic nerve acts to contract the detrusor muscle and thus
stimulate micturition
Describe what occurs during micturition
- As the bladder fills pressure increases
- stimulates stretch receptors in the bladder wall.
- afferent neurons from receptors enter the spinal cord and stimulate the parasympathetic neurons (pelvic splanchnic nerve S2-S4)
- Causes the detrusor muscles to contract
- Change in shape of detrusor muscle pulls open internal urethral sphincter
- afferent input at the same time inhibits the sympathetic neurons (Hypogastric nerve T1-L2) to the internal urethral sphincter, further contributes to opening
- afferent also inhibit somatic motor neurons pudendal nerve S2-S4 to the external urethral sphincter, relaxation
- Opening of both sphincters and contraction of detrusor muscles able to produce urination
Which nerve provides parasympathetic supply to the muscles of the bladder?
• ParaSympathetic - Pelvic Splanchnic nerve (S2-S4)
Which nerve provides sympathetic supply to the muscles of the bladder?
• SympathetiC - HypogastriC (T1-L2)
Which nerve provides somatic motor supply to the muscles of the bladder?
• Somatic Motor - Pudendal (S2-S4)
What is the role of the hypogastric nerve (T12-L2) in muscle control of the bladder?
- sympathetic
- HYPOGASTRIC NERVE (T12-L2) - causes the relaxation of the detrusor
muscle - promoting urine retention
What is the role of the pelvic splanchnic nerve (S2-S4) in muscle control of the bladder?
- parasympathetic
- increased signals from this nerve causes
contraction of the detrusor muscles - thereby stimulating micturition
What is the role of the pudendal nerve (S2-S4) in muscle control of the bladder?
- somatic motor control
- innervates the external urethral sphincter made of skeletal muscle
- it can cause it to constrict (storage phase) or relax (micturition)
Are there sensory (afferent) nerves from the bladder that report to the brain?
Yes
located in the bladder wall they signal the need to urinate when the
bladder becomes full
What is the function of the Urinary tract?
- To collect urine
- Store it under safe LOW-PRESSURE conditions
- Store it until it is socially acceptable to release urine
Define bladder compliance
Bladder to hold urine at low pressure via receptive relaxation - detrusor (T12-L2)
Define bladder voiding
- Voluntary complete emptying
Name three consequences of bladder dysfunction
• Consequences of bladder dysfunction:
- Incontinence
- Infection & bladder stones
- Upper urinary tract injury - due to high pressure etc.
Describe the voiding reflex
- intense bladder-afferent firing to pelvic nerve
- triggers spinobulbospinal reflex
- afferent signals passed to PAG (relay centre) via A-delta fibres
- PAG stimulates the pontine micturition centra
- PMC acts as an on/off switch
- PMC causes parasympathetic outflow to the bladder
- inhibits sympathetic and pudendal outflow
What is the periaqueductal grey?
A visceral and somatic control centre for the lower urinary tract.
What fibre input does the periaqueductal grey receive?
A delta fibres.
What is urinary incontinence?
The involuntary release of urine.
Name 2 types of incontinence.
- Stress incontinence.
2. Urge incontinence.
What can stress incontinence be due to?
Sneezing, coughing, exercise.
What can cause urge incontinence (desire to urinate)?
Any irritation to the bladder or urethra e.g. a bacterial infection.
Where does meiosis occur in the male testes?
Seminiferous tubules
Give two ways that the scrotum is cooled for spermatogenesis?
Air circulating around the scrotum and by a heat exchange mechanism in the blood vessels supplying the testes - the pampiniform plexus
If we look at a magnified cross-section of the testes what would we see as we go closer to the centre of the seminiferous tubules?
- central fluid-filled lumen contains the mature spermatozoa and around the diameter, there are spermatogonia and spermatocytes, gets mature as we reach the centre
What are the undifferentiated germ cells called in spermatogenesis?
Spermatogonia
When do spermatogonia begin to divide via mitosis
At puberty
What two cells do spermatogonia divide into?
Type A and Type B spermatogonium
Which type of spermatogonia remains outside the blood testicle barrier?
Type A spermatogonia
What is the role of Type A spermatogonia?
Constantly undergo mitosis to produce more daughter cells until death
What do spermatogonia differentiate into via mitosis?
Type A spermatogonia and Type B spermatogonia
What is the role of type B spermatogonia and what do they produce?
differentiate into primary spermatocytes and move through the blood testes barrier towards the lumen of the seminiferous tubules - new tight junctions form behind these Sertoli cells
What is produced after meiosis 1 of primary spermatocyte?
2 secondary spermatocytes
What is produced after meiosis 2 of secondary spermatocytes?
4 spermatids
Describe spermiogenesis
transformation of spermatids into spermatozoa
- sprouts tail and discards cytoplasm to become lighter
- the cytoplasm of the Sertoli cells around the
sperm retracts and the sperm are released into the lumen to be bathed in luminal
fluid
Describe the hypothalamic-pituitary-gonadal axis of the male reproduction system
- Hypothalamus secretes GnRH (gonadotrophin-releasing hormone)
- GnRH travels to the anterior pituitary hypothalami-hypophyseal
portal vessels and triggers the release of both LH & FSH - • FSH primarily acts on the Sertoli cells to stimulate the secretion of paracrine
agents required to initiate SPERMATOGENESIS - LH acts primarily on the Leydig cells to stimulate TESTOSTERONE secretion:
- testosterone diffuses from interstitial spaces to the seminiferous tubules.
- testosterone then enters the Sertoli cells
- where it
is able to facilitate SPERMATOGENESIS
Describe the negative feedback mechanism in the hypothalamic-pituitary-gonadal axis
- Testosterone INHIBITS LH secretion in two
ways:
1. Acts on the hypothalamus to decrease
the amplitude of GnRH bust resulting in a
decrease in the secretion of GnRH
2. Acts directly on the anterior pituitary
gland to decrease LH response to
GnRH - Sertoli cells (stimulated by FSH) release a
protein hormone called INHIBIN which acts on
the anterior pituitary to inhibit the release of
FSH
What changes does the sperm make with regards to its structure?
- It discards excess cytoplasm.
- Grows flagellum.
- Lots of mitochondria.
- Acrosomes at its head.
What is the role of the acrosomes
a protein-filled vesicle
containing enzymes to penetrate the egg
what is the role of the flagellum
Most of the tail is flagellum - a group of
contractile filaments that produce
a whiplike movement capable of propelling
the sperm at a velocity
how long do the spermatozoa spend in the testes?
40 to 60 days
Describe the efferent ductules in the male reproductive tract
- 12 small ciliated ducts collecting sperm from the rete testes and transporting to the epidydimis
Describe the epididymis
6m long coiled duct adhering to the posterior of testis
- site of sperm maturation and storage for 40-60 days
Describe the vas defrens
- muscular tube - 45 cm long
- from the scrotum through the inguinal canal to the posterior surface of the bladder
- widens into the terminal ampulla
describe the ejaculatory duct
- 2cm duct formed from ductus deferens and seminal vesicles passing through prostate to empty into the urethra.
What proportion of ejaculate is spermatozoa?
10%
90% prostatic and seminal secretions
Name three ducts that produce secretions that contribute to the production of ejaculate
bulbourethral
prostate gland
Seminal vesicle
How does the father decide the sex of the baby
Either X or Y sperm that fertilises the egg
What is the function of GnRH?
It acts on the anterior pituitary gland stimulating it to release FSH and LH.
Describe endocrine glands?
are ductless and release hormones directly into the blood
Where is the thyroid gland located?
anterior neck between C5 and T1 on top of the trachea
describe the structure of the thyroid gland
Have two lobes joined by a narrow isthmus
Which neck muscles does the thyroid lie behind?
Sternohyoid & sternothyroid
Name the two arteries which supply the thyroid
superior and inferior thyroid arteries
Which artery is the superior thyroid artery a branch of?
external carotid artery
Which artery is the inferior thyroid artery a branch of?
the thyrocervical trunk which in turn is a branch of the subclavian artery
Describe the nervous innervation of the thyroid gland
Branches from the sympathetic trunk
Does sympathetic innervation control hormone release?
No, the pituitary gland controls hormone release
Embryology: Where and when do the thyroid glands first appear?
Appear at 3-4 weeks
appear as an epithelial proliferation at the base of the pharynx under the tongue and migrates down towards larynx
Embryology: when do the thyroid glands first start secreting thyroxine?
at 18-20 weeks
Name the two functional units of the thyroid glands and their functions?
Follicular cells - produce hormones T3 and T4
C cells - produce calcitonin for Ca2+ homeostasis
What does the thyroid hormone affect?
Increased metabolism, increased sympathetic action, heat production, essential for growth and development too.
What is the common name for T4?
Thyroxine.
What is the full name of T3?
Triiodothyronine.
How many iodine molecules does triiodothyronine contain?
3.
Which molecule is active T3 or T4?
T3
More T4 is produced than T3 in the thyroid. What process produces T3 elsewhere?
As T3 is more active it can be produced peripherally from the conversion of T4.
Briefly describe oogenesis
- Oogonia stop dividing around 7th month of gestation
- during foetal life all of the oogonia differentiate into primary oocytes
- Meiosis 1 begins in utero before 12 weeks
- meiosis is arrested at metaphase 1 until puberty
- resumption after puberty only eggs destined for ovulation will complete meiosis 1
- first polar body produced
- meiosis 2 where the secondary oocyte becomes an ovum
- meiosis 2 is arrested at metaphase 2 until fertilisation
How many secondary oocytes does each primary oocyte yield?
1 secondary oocyte and 1 non-functional polar body.
What are the start and end products of mitosis in oogenesis?
Start: oogonia.
End: primary oocyte.
What are the start and end products of meiosis in oogenesis?
Start: primary oocyte.
Middle: secondary oocyte.
End: 1x ovum.
Describe the hormonal changes that occur at puberty.
- Increased amplitude of GnRH and GHRH.
- Increased levels of FSH, LH and sex steroids.
- Increased levels of growth hormone.
What factors can influence puberty?
- Nutrition (body mass).
- Leptin, insulin (hormones).
- Genetics.
- Exercise.
- Socio-cultural.
What are the 2 phases of the menstrual cycle?
- The follicular phase.
- The luteal phase.
The phases are approximately equal in length and are separated by ovulation.
Describe the follicular phase very briefly
- During which mature/Graafian follicle & secondary oocyte develop
Describe the luteal phase very briefly
- Beginning after ovulation and lasting until the death of the corpus
luteum
What do follicles begin as?
primordial follicles
What does a primordial follicle consist of?
- One primary oocyte
- thin layer of granulosa cells
What do granulosa cells secrete?
- Oestrogen
- Small amounts of progesterone just before ovulation
- Peptide hormone inhibin
What does the primordial follicle develop into?
primary follicle
What happens during the development of the primary follicle?
- oocyte increases in size
- oocyte becomes separated from the granulosa cells by the zona pellucida
- cytoplasmic processes and gap junctions allow for oocyte communication
What is the role of the zona pellucida?
- The zona pellucida contains glycoproteins that play an important role in the
binding of a sperm cell to the surface of the egg after OVULATION
What does the primary follicle develop into?
Preantral follicle
Describes what occurs during the development of the early antral follicle?
- primary oocyte reaches full size
- Fluid-filled space called the antrum begins to form due to fluid secreted by granulosa
What does the preantral follicle develop into?
early antral follicle
Describes what occurs during the development of the preantral follicle?
- mitosis of granulosa cells, increase in size
- connective tissue surrounding the granulosa cells differentiate into theca cells
- theca cells function together with granulosa cells to synthesise oestrogen
Approx how many early antral or preantral follicles begin to develop into larger antral follicles at the start of the menstrual cycle?
10-25
At what point in the cycle is the dominant follicle chosen and how?
- One week into the cycle further selection
- only one of the larger antral follicles - the dominant follicle begin to develop
What happens to the non-dominant follicles?
- Atresia - enlarge then degeneration - apoptosis
What happens to the dominant follicle as ovulation approaches?
- primary oocyte emerges from its meiotic arrest ( due to LH surge)
- completes first meiotic division to become a secondary oocyte
Describe what occurs during ovulation?
- the mature follicle becomes so large it balloons out onto the surface of the ovary
- thin walls of the follicle rupture
- secondary oocyte surrounded by zona pellucida and granulosa cells carried out of the ovary by the antral fluid at Day 14
What happens to the Graafian follicle after the discharge of egg and antral fluid?
- Rapid transformation
- Granulosa cells enlarge and a gland-like structure called corpus luteum forms
What does the corpus luteum secrete?
Oestrogen
large amounts of progesterone
- inhibin
What happens to the corpus luteum when the discharged egg is not fertilised?
Corpus luteum fully developed at 10 days
- rapid apoptosis that triggers menstruation
- degenerates into the corpus albucans.
Where and when is oestrogen synthesised and released before ovulation?
Follicular phase
- granulosa cells
Where and when is oestrogen synthesised and released after ovulation?
luteal phase
- corpus luteum
Where and when is progesterone synthesised and released before ovulation?
released in small amounts by granulosa and theca cells
What is the major source of progesterone after ovulation?
Corpus luteum
Name five factors released that affect the ovary
GnRH, FSH, LH, Oestrogen &
Progesterone
What is FSH required for in follicular development?
development of the follicle beyond preantral & early antral
- granulosa cells multiply and produce oestrogen
Menstrual cycle: why do LH and FSH levels decrease after ovulation?
They are inhibited by the high progesterone and oestrogen concentrations.
Menstrual cycle: why do FSH levels increase at the end of the cycle?
The fall in progesterone and oestrogen concentration means FSH is no longer inhibited and so its plasma concentration begins to rise
Which cells does FSH act on in the follicle?
Granulosa cells
What is the affect of oestrogen on the granulosa cells?
Paracrine/autocrine agent
- along with FSH and growth factors stimulates proliferation of granulosa cells
- further oestrogen production
What is the function of theca cells?
They produce androgens (oestrogen precursors) which diffuse into granulosa cells to form oestrogen.
Describe the hypothalamo-pituitary-ovarian-axis?
GnRh from hypothalamus acts on the anterior pituitary to release LH and FSH. LH acts on theca cells stimulating androgen release. Androgen diffuses from theca to granulosa. FSH acts on granulosa cells stimulating the conversion of androgen into oestrogen (aromatase enzyme). Inhibin is also released from granulosa cells. Inhibin and oestrogen have a negative feedback affect on the hypothalamus and anterior pituitary.
Menstrual cycle: what is the effect of decreasing FSH levels in the follicular phase?
Decreasing FSH levels cause the non-dominant, immature follicles to degenerate.
Why does the development of the dominant follicle decrease FSH?
Dominant follicle starts to produce more Oestrogen
- negative feedback on the secretion of gonadotrophins for both anterior pituitary and hypothalamus
Why does the FSH level decrease more than the LH levels?
Granulosa cells also secrete inhibin
- inhibits mainly the secretion of FSH
Menstrual cycle: what is the effect of oestrogen at high levels on the gonadotropins?
At high levels oestrogen exerts positive feedback on gonadotropin secretion, this stimulates the LH surge.
Menstrual cycle: what is the effect of the LH surge?
Stimulates ovulation.
- stimulates the remaining granulosa and theca cells of the follicle to turn into the corpus luteum
What does LH act on in follicles?
Theca cells
What is the effect of LH on theca cells?
Proliferation
- synthesise androgens
- diffuse to granulosa cells and converted to oestrogen by aromatase
What are two things are needed for the secretion of oestrogen by granulosa cells?
both granulosa and theca cells
- both pituitary gonad gonadotrophins
Which cells bear similarities to Leydig cells in males and why?
theca cells
- synthesise mainly androgens
- stimulated by LH
Which cells bear similarities with Sertoli cells in females and why?
Granulosa cells
- controls the microenvironment in which the germ cell matures and develops
- Stimulated by FSH and oestrogen
When is the concentration of inhibin the highest?
luteal phase
- increases during the late follicular phase
What is the effect of large amounts of oestrogen on the anterior pituitary and hypothalamus?
- anterior pituitary to INCREASE the SENSITIVITY of LH-releasing
cells to GnRH (from the hypothalamus) - a POSITIVE FEEDBACK MECHANISM
• The net result is that the rapidly rising oestrogen leads to the LH surge
Which gonadotrophin is needed to maintain the function of the corpus luteum?
- Low LH concentration
What causes the corpus luteum to degenerate into corpus Albicans?
Absence of an increase in gonadotrophins
When the corpus luteum degenerates what happens to the concentration of Progesterone, oestrogen, LH and FSH?
- progesterone and oestrogen decreases
- increased FSH and LH due to removed negative feedback
What phase starts from Day 1 of the menstrual cycle?
Menstrual phase
What stimulates the menstrual phase?
withdrawal of progesterone- degeneration of corpus luteum
What can be seen histologically in the menstrual phase?
stromal haemorrhage
- granulocytes in stroma
- stromal and glandular fragmentation
how long does the menstrual phase last?
3-5 days
What is the next phase after the menstrual phase and when does it occur?
From day 5 for around 10 days
- proliferative phase
- between the cessation of menstruation and start of ovulation
What happens in the proliferative phase?
- menstrual flow decreases and endometrium begins to thicken under the influence of oestrogen
- oestrogen causes growth of endometrium and myometrium
- oestrogen also indices the synthesis of progesterone receptors in endometrial cells
Describe the histological appearance of the proliferative phase
• Straight gland —oestrogen stimulation—> mitotic activity —> tortuous glands • No luminal secretions • Stromal cells; spindled, compact, show mitotic activity
which follicle phase corresponds to the menstrual and proliferative phases?
Follicular phase
Which phase comes after the proliferative phase and when?
Secretory phase
- between ovulation and the onset of the next menstruation
Under the influence of which factors does the secretory phase occur?
progestrone and oestrogen
What occurs in the secretory phase?
endometrium begins to secrete glycoproteins and glycogen from glandular epithelium
- progesterone acts upon the endometrium to convert it into active secreting tissue to make it a hospitable environment for implantation and nourishment for the embryo
- Progesterone also inhibits myometrial contractions by opposing oestrogen important for fertilised egg to safely implant in uterus
Describe the histological appearance of the secretory phase
• Early: sub-nuclear vacuoles • Mid: - Vacuoles above & below nucleus - Intraluminal secretions (pink) - Rounded glands - Stromal oedema • Late: - Spiral arteries in stroma - Elongated, saw-soother glands with increased luminal secretions
which follicle phase corresponds to the secretory phase?
Luteal phase
What are the effects of progesterone and oestrogen on the secretion of mucus in the cervix?
Oestrogen alone causes the mucus to be clear and watery at the time of ovulation to allow sperm to move through the cervix easily
- significant amounts of progesterone after ovulation cause the mucus to become thick and sticky forming a plug which prevents bacteria entering the uterus - protects the embryo
summarise the menstrual cycle
- Days 1-5 - oestrogen and progesterone are low because of the corpus luteum regression, endometrium lining sloughs, and more secretion of FHS and LH therefore several growing follicles are stimulated to mature (menstrual phase)
- day 7 a single follicle becomes dominant
- 7-12 / Oestrogen increases because of dominant follicle therefore endometrium proliferates
- 7-12/ LH and FSH decrease due to oestrogen and inhibin negative feedback, therefore atresia of non-dominant follicles
- 12-13 LH surge induced by plasma oestrogen, therefore, oocyte induced to complete first meiotic division and follicle stimulated to release digestive enzymes
- day 14/ ovulation
- day 15-25/ corpus luteum forms under the action of low but adequate LH, it secretes oestrogen and progesterone therefore secretory endometrium forms and secretion of FSH and LH is inhibited no new follicles develop
- day 25-28/ corpus luteum degenerates if no implantation therefore oestrogen and progesterone concentrations decrease therefore endometrium begins to slough and a new cycle begins
Menstrual cycle: what causes oestrogen levels to rise in the follicular phase?
Oestrogen is released from granulosa cells and also from the developing and dominant follicle.
Menstrual cycle: what is the effect of oestrogen at low levels on the gonadotropins?
At low levels oestrogen inhibits gonadotropin release.
Menstrual cycle: what is the effect of decreasing FSH levels in the follicular phase?
Decreasing FSH levels cause the non-dominant, immature follicles to degenerate.
Menstrual cycle: what is the effect of oestrogen at high levels on the gonadotropins?
At high levels oestrogen exerts a positive feedback on gonadotropin secretion, this stimulates the LH surge.
Menstrual cycle: why do progesterone and oestrogen levels increase following ovulation?
The ruptured follicle has transformed into a corpus luteum which releases large amounts of progesterone and oestrogen.
Menstrual cycle: why do LH and FSH levels decrease after ovulation?
They are inhibited by the high progesterone and oestrogen concentrations.
Menstrual cycle: what is the importance of the low LH concentration in the luteal phase?
Low but adequate LH acts to maintain the corpus luteum.
Menstrual cycle: what causes oestrogen and progesterone concentrations to fall towards the end of the luteal phase?
The corpus luteum degenerates into the corpus albicans if fertilisation does not occur. Therefore progesterone and oestrogen are no longer released.
Menstrual cycle: why do FSH levels increase at the end of the cycle?
The fall in progesterone and oestrogen concentration means FSH is no longer inhibited and so its plasma concentration begins to rise.
Menstrual cycle: why does the corpus luteum not degenerate if fertilisation occurs?
When the blastocyst implants the invading trophoblast cells release human chorionic gonadotropin (hCG). This acts to maintain the corpus luteum throughout pregnancy.
In order for pregnancy to occur when must the introduction of sperm occur?
Between 24-48 hours of fertilisation as the egg only stay viable for this time
Sperm can remain capable for fertilisation till 4-6 days
Describe how the egg is transported to the fallopian tube
- ovulation extruded onto the surface of ovaries
- smooth muscle of the fimbria at the end of the fallopian tube causes the fimbria to pass over the ovary while the cilia beat inwards
- the ciliary movement sweeps the egg into the fallopian tube
- once inside the fallopian tube the cilia are slow and it takes around 4 days for the egg to be beaten into the uterus.
Describe sperm transport into the fallopian tube
- Ejaculation results in the deposition of semen into the vagina during
intercourse - Fluid pressure of the ejaculate helps the sperm travel out of the vagina into the cervix
- passage through cervical mucus is dependant on the release of oestrogen causing mucus to be watery to enable sperm to easily travel through it
- Sperm travels through into the uterus and fallopian tube using its flagella for propulsion
Why is sperm mortality extremely high during the trip from the vagina to the fallopian tube?
- Vaginal environment is acidic to protect against yeast and bacterial infections
- The length and energy requirements for the trip is very large for the sperm
- reason why ejaculate contains so many sperm to increase the chance of fertilisation
Once the sperm has reached the fallopian tube can they fertilise the egg straight away?
No, they must mature and reside in the fallopian tube for several hours to be acted upon by secretions of the tract
Describe what occurs during capacitation
The final stage of sperm maturation occurs in the female genitalia. Before this spermatozoa would be unable to fertilise an oocyte.
What does capacitation cause?
- The previous wavelike beats of the sperms tail to be replaced by a more
whip like action that will propel the sperm forward in stronger surges - The sperms plasma membrane to become altered so that it will be
capable of fusing with the surface membrane of the egg
Where does fertilisation occur?
- Ampulla of the fallopian tube
What in particular does the sperm bind to during fertilisation?
- Zona pellucida
What is the role of the zona pellucida during fertilisation?
- glycoproteins present act as receptors for sperm surface proteins
- Triggers the acrosome reaction
What is the acrosome reaction?
Many sperm move through granulosa cells to bind with the zona pellucida. This binding triggers acrosomal enzymes from the sperm’s head to digest through the zona pellucida. The sperm advances through; the first sperm to penetrate the entire zona pellucida and to reach the egg’s plasma membrane will fuse. now called a zygote
What is the function of block to polyspermy?
It is a mechanism to prevent the entry of additional sperm fusing with the egg.
Describe the mechanism of the block to polyspermy.
Cortical reaction initiated by
- The egg releases contents of secretory vesicles by exocytosis.
- Enzymes from the vesicles enter the zona pellucida and inactivate sperm binding sites and harden the zona pellucida
When does meiosis 2 occur?
4-7 hours after gamete fusion when the zygote is still in the fallopian tube
How long does the zygote remain in the fallopian tube?
3-4 days
Why does the zygote stay in the fallopian tube for 3-4 days?
• The main reason for this is that oestrogen maintains the contraction of the
smooth muscle near where the fallopian tube enters the uterus (essentially
holding the zygote in the fallopian tube - as plasma progesterone levels
increase, this smooth muscle relaxes and allows the zygote to pass
through the fallopian tube
What is cleavage?
24 hours after fertilisation mitotic divisions, no cell growth, increase totipotent cell numbers
What is compaction phase in development ?
Day 4 - cells flatten and maximise intracellular contacts, tight junctions, essential in being able to differentiate quickly
What occurs during cavitation and differentiation?
Day 5 - Fluid-filled cavity expands to form BLASTOCYST
- BLASTOCYST is defined as having greater than
80 cells - these cells have lost their
totipotentiality and have begun to differentiate
- Blastocyst consists of an outer layer of cells
known as the trophoblast, an inner cell mass & a
central fluid-filled cavity
What occurs to the blastocyst during expansion?
day 5-6
- Cavity expands further and the diameter of the blastocyst increases and the
zona pellucida THINS
what occurs during hatching?
Day 6+
- Blastocyst expansion & enzymes result in the hatching of the embryo from the
zona pellucida
necessary for implantation
Describe implantation.
The blastocyst implants into the endometrium on day 6. The trophoblast cells overlying the ICM invade the endometrium. Nutrient rich endometrial cells provide the metabolic fuel for early embryo growth until the placenta takes over.
What is secreted to prevent antigenic rejection of the embryo?
interleukin-2
describe the development of the placenta
the 8-cell morula arrives in the uterus and develops into the blastocyst.
- the outer cell layer - trophoblasts cell mass invades the endometrium which degenerates and the trophoblasts are in contact with the stroma
What day is implantation usually complete by?
11 days post ovulation
What can the trophoblast differentiate into during implantation?
Cytotrophoblast
• Syncitiotrophoblast (erodes endometrial blood vessels - using proteolytic
enzymes)
What is the role of the cytotrophoblast?
Forms solid masses covered by syncytiotrophoblast - primary chorionic villi. These masses become filled with stroma, forming secondary chorionic villi. Capillaries appear in the stroma – tertiary chorionic villi.
What is the role of the syncytiotrophoblast?
Uptake of oxygen and nutrients from the maternal blood.
Release of CO2 and waste products into the maternal blood. The exchange surface is gradually increased during maturation due to the branching of the villi.
What is the Chorion?
The embryonic portion of the placenta supplied by the outermost layer of trophoblast cells
What are the chorionic villi?
finger-like projections of the trophoblast cells extend from the chorion to the endometrium
- contain a rich network of capillaries that are part of embryos circulation
- endometrium around villi is altered by enzymes from invading villi so each villi is surrounded by a pool of maternal blood
through which vessels does the maternal blood enter the placental sinuses?
UTERINE
ARTERY; the blood flows through the sinuses and then exits via the UTERINE
VEINS
Which vessels transport blood from the foetus into the capillaries of the chorionic villi?
Umbilical arteries and out of capillaries back into the foetus via the umbilical vein - all umbilical vessels contained with the umbilical cord
What is the decidua basalis?
A part of the endometrium invaded by trophoblast
What is the decidua capsularis?
A part of the endometrium overlying the blastocyst
What is the decidua parietalis?
Endometrium lining the rest of the uterine cavity.
What invades the decidua basalis?
Syncytiotrophoblast.
Why is it important that the chorionic villi branch in maturation?
Branching increases the surface area for the exchange of nutrients.
What does the placenta provide for the developing foetus
- Nutrition
- Gas exchange
- Waste removal
- Endocrine & immune support
what are the three main functions of the placenta?
- Placental metabolism (synthesises glycogen, cholesterol and fatty acids) to provide nutrients and energy
- transport, transports - Gases & nutrition; O2 & CO2 - to & from baby, CO
- Water
- Glucose (facilitated diffusion via hexose transporters)
- Vitamins
- Amino acids - by active transport
- Hormones, mainly steroid NOT PROTEIN
- Electrolytes
- Maternal antibodies IgG and NOT IgM
- Waste products; urea, uric acid & bilirubin (conjugated is poorly
transported but unconjugated from foetus crosses placenta easily) - Drugs and their metabolites - can result in fetal drug addiction
- Infectious agents