Repro Flashcards
After colonising the gonad, what must germ cells do in order to complete gametogenesis?
Proliferate by mitosis
Reshuffle genetically and reduce to haploid by meiosis
Cytodifferentiate into mature gametes
List some basic differences between the nature of oocyte production and spermatogenesis
Oocytes - very few gametes (about 400 in lifetime), intermittent production (about 1 a month)
Spermatogenesis - huge number, (about 200 million/day), continuous production, essentially ‘disposable’ cells
What are the 2 main functions of meiosis?
Reduce the chromosome number in gamete to 23, and ensure every gamete is genetically unique
When is meiosis used?
Only in the production of eggs and sperm
Briefly outline the process of meiosis
Two successive cell divisions, meiosis 1 and meiosis 2, producing 4 daughter cells
How does meiosis differ in females?
Only 1 daughter cell develops into a mature oocyte, others form polar bodies
How do genetic variations arise?
Crossing over - exchange of regions of DNA between 2 homologous chromosomes
Random segregation - distribution of chromosome among 4
Independent assortment - 2 homologous chromosomes of a pair must go into separate gametes
Why is there a blood-testes barrier?
There is different genetic material in sperm, so may be attacked by the immune system
What do Sertoli cells do?
Nurse/nurture cells
What is the Sertoli cell barrier also referred to as?
Blood testes barrier
What are spermatogonia?
Male germ cells - the ‘raw material’ for spermatogenesis
What can spermatogonia divide into?
Ad spermatogonium (maintain stock) Ap spermatogonium (give rise to primary spermatocytes)
Describe the sequence of division by meiosis by primary spermatocytes
Primary spermatocytes - secondary spermatocytes - spermatids
What is spermiogenesis?
The process by which a primary spermatocyte forms 4 haploid spermatids, which differentiate into spermatozoa
List the sequence of cells produced in spermiogenesis
Spermatogonium - primary spermatocyte - secondary spermatocyte - spermatid - spermatozoa (sperm)
How is the spermatogenic cycle defined?
The time taken for reappearance of the same stage within a given segment of tubule (approx 16 days in a human)
What is the spermatogenic wave?
The distance between the same stage along a tubule.
Waves follow a corkscrew like spiral towards the inner part of the lumen
How are sperm transported to the epididymis?
Non-motile - transport via Sertoli cell secretions, assisted by peristaltic contraction, until they reach the epididymis
How do spermatids become spermatozoa?
Spermatids are released into lumen of seminiferous tubules (spermiation). They remodel as they pass down seminiferous tubule, through rete testes and ductuli efferentes and into the epididymis to finally form spermatozoa.
Approximately how much fluid is in ejaculate?
2ml
What are the seminal vehicle secretions constituted of?
Amino acids, citrate, fructose, prostaglandins
70%
What proportion of ejaculate is seminal vesicle secretions?
Approx 70%
What proportion of ejaculate is secretions of prostate?
Approx 25%
What constitutes the prostatic portion of ejaculate?
Proteolytic enzymes, zinc
What proportion of ejaculate is sperm? (Via vas deferens)
2-5%
How many sperm are approximately in an ejaculate?
200-500 million per ejaculate
What proportion of ejaculate is bulbourethral gland secretions?
Less than 1% total volume
What constitutes bulbourethral gland secretions in ejaculate?
Mucoproteins, help to lubricate and neutralise acidic urine in distal urethra
What is sperm capacitation?
The final maturation step required for sperm to become fertile, stimulated by the conditions in the female genital tract.
What are the steps of capacitation, stimulated in spermatids by the conditions of the female genital tract?
Removal of glycoproteins and cholesterol from sperm membrane
Activation of sperm signalling pathways (atypical soluble adenylyl cyclise and PKA involved)
Allow sperm to bind to zona pellucida of oocyte and initiate acrosome reaction
What must first be done to sperm before it can be used for IVF?
Must be incubated in capacitation media
Where do germ cells arise from?
The yolk sac
Describe the migration of female germ cells embryologically
Germ cells arise from yolk sac, colonise the gonadal cortex and differentiate into oogonia (single oogonium). Oogonia then proliferate rapidly by mitosis. By end of 3rd month, oogonia arranged in clusters surrounded by flat epithelial cells. Majority continue to divide by mitosis, but some enter meiosis (arrest in prophase of meiosis 1 and are called primary oocytes)
Embryologically, what has happened to female gametes by the end of the 3rd month?
By end of 3rd month, oogonia arranged in clusters surrounded by flat epithelial cells. Majority continue to divide by mitosis, but some enter meiosis (arrest in prophase of meiosis 1 and are called primary oocytes).
When is the max number of germ cells reached in the female?
By mid gestation (approx 7 million)
Cell death then begins, and many oogonia and primary oocytes degenerate (atresia)
What occurs after the max no. Of germ cells has been reached in the female, embryologically?
Cell death then begins, and many oogonia and primary oocytes degenerate (atresia)
What embryologically has occurred with regards to gametes in the female by 7 months?
The majority of oogonia have degenerated. All surviving (approx 2 million) primary oocytes have now entered meiosis 1 and are individually surrounded by layer of flat epithelial cells, called follicular cells - now called primordial follicle
When does maturation of oocytes continue in the female, post birth?
Puberty
Approximately how many oocytes remain in the female by puberty?
Approx 40,000
Most undergo atresia during childhood
What are the 3 phases of oocyte maturation?
1 - preantral
2 - antral
3 - preovulatory
Approximately how many oocytes start to mature each month from puberty onwards?
Approx 15-20
Preantral stage - What changes occur to the surrounding follicular cells of primordial follicles, as they begin to grow?
Change from flat to cuboidal, and proliferate to produce a stratified epithelium of granulosa cells
Describe the antral stage
As development continues, fluid filled spaces appear between granulosa cells. These coalesce to form the Antrum. Several follicles begin to develop with each ovarian cycle. Usually one reaches maturity (rest become atretic)
What is the 1st polar body?
Meiosis 1 completes, producing 2 haploid daughter cells. One receives most of cytoplasm, the other receives practically none, and is a rememant (called the 1st polar body)
Describe the preovulatory phase?
Surge in LH induces preovulatory growth phase. Cell has now completed meiosis1 and enters meiosis 2, but arrests in metaphase approx 3hrs before ovulation. Meiosis 2 is only completed if oocyte is fertilised, otherwise cell degenerates approx 24hrs after ovulation.
Describe the ovulation stage
FSH and LH stimulate rapid growth of follicle several days before ovulation. Mature follicle now approx 2.5 cm in diameter and called gracfian follicle. LH surge increases collagenase activity. Prostaglandins increase response to LH and cause local muscular contraction in ovarian wall. Oocyte extruded and breaks free from ovary.
What is the corpus luteum ?
Remaining granulosa and theca interna cells become vascularised. Develop yellowish pigment and change into lutein cells, which form the corpus luteum.
What does the corpus luteum do?
Secretes oestrogens and progesterone
Stimulates uterine mucosa to enter secretory stage in preparation for embryo implantation.
Dies after 14 days if no fertilisation occurs
Describe oocyte transportation
Shortly before ovulation, fimbriae sweep over surface of ovary. Uterine tube begins to contract rhythmically. Oocyte carried into tube by sweeping movements of fimbriae and by motion of cilia on epithelial lining.
Oocyte then propelled by peristaltic muscular contractions of the tube and by cilia in the mucosa. If fertilised, oocyte reaches uterine lumen in 3-4 days
What happens to the corpus luteum if no fertilisation occurs?
Corpus luteum degenerates. Forms mass of fibrotic scar tissue, the corpus albicans. Progesterone production decreases, precipitating menstrual bleeding.
What happens to the corpus luteum if fertilisation does occur?
Degeneration of corpus luteum prevented by human chorionic gonadotropin, secreted by the developing embryo. The corpus luteum continues to grow and forms the corpus luteum of pregnancy (corpus luteum graviditatis). Cells continue to secrete progesterone until approx 4th month, secretion of progesterone by placenta then becomes adequate.
Briefly describe hormonal control of the ovarian cycle
Under influence of GnRH, anterior pituitary releases FSH and LH. Follicles stimulated to grow by FSH, and to mature by FSH and LH. Ovulation occurs on LH surge. LH also promotes development of corpus luteum.
Approximately how many sperm are formed a day?
Approx 200 million
How are sperm formed, very basically?
4 spermatids formed with no polar body formation and equal division of cytoplasm.
When does spermatogenesis begin?
Puberty, continues throughout adult life
Where does spermatogenesis occur?
All stages complete in testes
At what rate does oogenesis occur?
Usually 1 ovum per 28 day menstrual cycle.
Very briefly outline oogenesis
1 ovum produced with unequal division of cytoplasm and 3 polar bodies produced.
When does oogenesis occur?
Starts in foetus, ends at menopause.
Where does oogenesis occur?
Ovaries, last stage of meiosis 2 occurs in oviduct.
What effect does corticotropin releasing hormone CRH have on the pituitary?
Stimulates ACTH secretion
What effect does thyrotropin releasing hormone TRH have on the pituitary?
Stimulates TSH and prolactin secretion
What effect does growth hormone releasing hormone GHRH have on the pituitary?
Stimulates GH secretion
What effect does somatostatin have on the pituitary?
Inhibits GH (+ other hormones) secretion
What effect does gonadotropin releasing hormone GnRH have on the pituitary?
Stimulates LH and FSH secretion
What effect does prolactin releasing hormone PRH have on the pituitary?
Stimulates PRL secretion
What effect does prolactin inhibiting hormone (dopamine) have on the pituitary?
Inhibits PRL secretion
What type of tissue is the anterior pituitary?
Not nervous tissue, an amalgam of hormone producing glandular cells. Stains darker, arises from Rathke’s pouch. Connected to the hypothalamus by the superior hypophyseal artery
What connects the anterior pituitary to the hypothalamus?
Connected to the hypothalamus by the superior hypophyseal artery
What 6 peptide hormones does the anterior pituitary produce?
Prolactin, GH, TSH, ACTH, FSH, LH
What constitutes the posterior pituitary?
Nervous tissue, stains lighter.
What is the anterior pituitary also called?
Pars distalis, adreno hypophysis
What is the posterior pituitary also called?
Pars nervosa, neuro hypophysis
What does the posterior pituitary secrete?
ADH (vasopressin - urinary) and oxytocin (important in reproduction)
What, essentially, is the posterior pituitary?
An overgrowth of the hypothalamus, composed of neural tissue. Hypothalamic neurons pass through the neural stalk and end in the posterior pituitary.
The upper portion of the neural stalk extends into the hypothalamus and is called the median eminence.
What does GnRH stimulate?
The anterior pituitary gland to secrete LH and FSH
Describe hypothalamic control of FSH and LH
One releasing hormone - GnRH
GnRH release is pulsatile, every 1-3 hrs. Intensity of GnRH stimulus is affected by frequency of release and intensity of release. GnRH travels to pituitary in hypophyseal portal system.
What size protein is GnRH
10 amino acids long
What controls the intensity of GnRH stimulus?
Intensity of GnRH stimulus is affected by frequency of release and intensity of release (pulsatile release every 1-3hrs)
What happens in the absence of GnRH?
Little or no FSH of LH release
What proportion of anterior pituitary cells secrete FSH and LH?
5-10% total anterior pituitary cells
What controls gonadotroph synthesis and release?
Positive and negative feedback by gonadal steroids and gonadal peptides. Controlled by gonadotroph cells in anterior pituitary.
How do gonadal hormones decrease gonadotrophin release?
Decrease GnRH release from hypothalamus and by affecting ability of GnRH to stimulate gonadotropin secreting from anterior pituitary
In the male, LH and FSH primarily work via which receptors?
GalphaS
PCR to adenylyl cyclase
In the male, upon which cells do LH and FSH primarily act upon?
Testicular sertoli cells, leydig cells
What effects do LH and FSH have in the male?
Stimulate sex hormones synthesis (steroidgenesis) and control gamete production
Where does LH act in the male, and what effect does it have?
Leydig cells of the testis, causing secretion of testosterone
Describe negative feedback of LH in the male
Negative feedback control - testosterone reduces LH from AP and reduces GnRH secretion, thus anterior pituitary LH and FSH decrease
What stimulates spermatogenesis?
FSH receptor activation on Sertoli cells of seminiferous tubules
What effects does FSH have on Sertoli cells?
Causes them to grow and secrete spermatogenic substances, but needs testosterone, which diffuses in to seminiferous tubules
What does inhibit do in the male?
Reduces FSH secretion selectively - related to developing gametes
Describe briefly the male HPG axis
In median long term testosterone levels constant
Circadian rhythm, highest early morning, and effects of environmental stimuli, driven by the brain
When are testosterone levels generally highest in the male?
Early morning
Via which receptors do FSH and LH act primarily on in the female?
GalphaS PCR (adenylyl cyclase)
Which cells do FSH and LH target in the female?
Ovarian granulosa cells, theca interna
What do FSH and LH stimulate in the female?
Stimulate sex hormone synthesis (steroidgenesis, oestrogen, progesterone, inhibin). Control gamete production (folliculogenesis and ovulation)
What does oestrogen do in the female?
Moderate titres of oestrogen reduce GnRH secretion (negative feedback)
High titres of oestrogen alone promote GnRH secretion (positive feedback, LH ‘surge’)
What effects does progesterone have in the female?
Increase inhibitory effects of moderate oestrogen
Prevents positive feedback of high oestrogen (no LH surge)
What effect does oestrogen have upon the pulses of GnRH?
Reduces GnRH quantity in pulse
What effect does progesterone have upon the pulses of GnRH?
Decreases the frequency of pulses
What effect does inhibin have on FSH in the female?
Inhibits the secretion of FSH. Has a small inhibitory effect on LH also
Where is inhibin released from in the female?
From granulosa cells of corpus luteum
What does the menstrual cycle enable the preparation of?
The gamete (ovarian cycle) The endometrium (uterine cycle)
What are the key points of the menstrual cycle?
Ovulation Waiting (pause, maintaining endometrium until a signal is received to indicate that fertilisation has occurred)
What controls the menstrual cycle?
Gonadotrophins (acting on the ovary) Ovarian steroids (acting on tissues of reproductive tract, to control the cycle)
Where do gonadotrophins act in the female?
Act on ovary, promoting follicular development and production of ovarian hormones (steroid hormones an inhibin). Controlled by effects of gonadal hormones (negative and positive feedback).
Describe the start of the menstrual cycle
No ovarian hormone production. Early development of follicles begins. Low steroid and inhibin levels. Little inhibition at the hypothalamus of anterior pituitary. Free from inhibition (FSH levels rising)
Describe the role of FSH at the start of the menstrual cycle
FSH binds to granulosa cells Follicular development continues Theca interna appears Follicle now capable of oestrogen secretion Inhibin secretion begins
Describe the mid follicular phase of the menstrual cycle
Need to nominate a dominant follicle, and prevent recruitment o any further follicles. 2 things happen.
Follicular oestrogen now at a concentration when it can exert POSITIVE feedback at the hypothalamus and anterior pituitary.
Gonadotrophin levels can rise - effect seen on LH only.
Follicular inhibin rising, selective inhibition on FSH production by anterior pituitary
What does inhibin do in the mid follicular phase in the female?
Follicular inhibin rising, selective inhibition on FSH production by anterior pituitary
Describe the preparation for ovulation phase of the menstrual cycle
Circulating oestradiol and inhibin rise rapidly - oestradiol production no longer dependent on FSH. Surge in LH production. Progesterone production begins (granulosa cells become responsive to LH). Modulation of GnRH pulse generator.
What effect does high oestradiol concentration have on the anterior pituitary?
Enhances sensitivity of anterior pituitary gonadotrophins to GnRH
Describe the ovulation phase of the menstrual cycle
Meiosis 1 completes and meiosis 2 starts.
Mature oocyte extruded through the capsule of the ovary.
After ovulation, the follicle is luteinised. Secreted oestrogen and progesterone in large quantities. Inhibin continues to be produced. LH is now suppressed because of negative feedback due to presence of progesterone. Further gamete development suspended - waiting phase established.
What inhibits LH production after ovulation?
The presence of progesterone, released by the follicle
Describe the luteal phase of the menstrual cycle
Corpus luteum produces progesterone and oestrogens from androgens. Produces inhibin (promotes production of progesterone). Regresses spontaneously in the absence of a further rise in LH
Describe the end of the menstrual cycle, in the absence of a pregnancy
In the absence of a further rise in LH, corpus luteum regresses. Dramatic fall in gonadal hormones. Relieving negative feedback. Resets to start again
Describe the end of the menstrual cycle, in the presence of a pregnancy
If fertilisation has occurred, syncytiotrophoblast produces human chorionic gonadotropin (approx same effect as LH). Exets luteinising effect
Describe what the corpus luteum does at the start of pregnancy to support it
Corpus luteum, supported by placental hCG, produces steroid hormones to support pregnancy. Eventually, the placenta is capable of production of sufficient quantities of steroid hormones to control the HPO axis throughout pregnancy
Describe the actions of oestrogen in the follicular phase
Fallopian tube function Thickening of endometrium Growth and motility of myometrium Think alkaline cervical mucus Vaginal changes Changes in skin, hair and metabolism
Describe the actions of progesterone in the luteal phase
Further thickening of endometrium into secretory form
Thickening of myometrium, but reduction of motility
Thick, acid cervical mucus
Changes in mammary tissue
Increased body temperature
Metabolic changes
Electrolyte changes
What is the normal duration of the menstrual cycle?
21-35 days
What are variations in menstrual cycle length due to?
Variation in length of follicular phase
What is the length of the luteal phase?
Strictly controlled to 14 +/- 2 days
What factors affect the menstrual cycle?
Physiological factors (pregnancy/lactation)
Emotional stress
Low body weight
What is thelarche?
Development of breast
What is puberarche?
Development of axillary pubic hair
What is menarche?
The first menstrual period
What is adrenarche?
The onset of an increase in the secretion of androgens
What is puberty?
When sexual maturation and growth are completed and result in ability to reproduce. Primary sexual characteristics established before birth, but reproductive system inactive until puberty
Describe th basic sequences of events in puberty
Accelerated somatic growth
Maturation of primary sexual characteristics (gonads and genitals)
Appearance of secondary sexual characteristics (pubic and exillary hair, female breast development, male voice change)
Menstruation and spermatogenesis begin
How is puberty initiated?
By the brain. Onset of puberty associated with steady rise in FSH and LH secretion, due to a rise in GnRH secretion.
What is early onset puberty also termed?
Precocious puberty
Describe the growth spurt in puberty
Occurs in both sexes. Earlier and shorter in girls, males larger as growth spurt longer and faster. Depends on growth hormones and steroids in both sexes.
What does the growth spurt depend on?
Depends on growth hormones and steroids in both sexes.
Why are males bigger, with regards to the growth spurt?
Growth spurt longer and faster. Oestrogen closes the epiphyses earlier in girls.
What ends the growth spurt?
Closing of the epiphyseal growth plates. Epiphyseal fusion. Oestrogen closes the epiphyses earlier in girls
What generally determines when a girl will undergo menarche?
Critical weight (usually 47kg)
What is the critical weight, at which girls generally undergo menarche?
47kg
What factors might influence when a girl undergoes menarche?
Significant weight loss (reproductive cycle ceases)
Nutrition important
Leptins may be involved in signalling
Body weight most important factor
What kind of tumours may influence puberty in humans?
Pineal tumours
What are the first changes seen in puberty?
Hormonal changes
Describe the hormonal changes seen during puberty
Increased stimulation of hypothalamo-pituitary-gonadal axis
Gradual activation of GnRH
Increased frequency and amplitude of LH pulses
Gonadotrophins stimulate secretion of sexual steroids (oestrogen and androgens)
Extragonadal hormonal changes (elevation of IGF-1 and adrenal steroids)
Describe the effects of GH secretion from the pituitary during puberty
Increased TSH
Increased metabolic rate
Promotes tissue growth
Increased androgens - retention of minerals in body to support bone and muscle growth
What is the first phenotypic changes seen in the female?
Breast development
What is the first phenotypic changes seen in the male?
Testicular enlargement
What is the very first changes that occur in puberty (proceeding phenotypic changes by several years)
Nocturnal GnRH pulsatory LH secretion
Sleep related LH increase, stimulates a nocturnal rise of testosterone/oestrogen
Why is there no gonadal function in young children?
Levels of LH and FSH are insufficient to initiate gonadal function
Describe the male hormonal changes that occur during puberty
LH and FSH increase at approx 10yrs
Adrenals also secrete androgens
Androgens initiate growth of sex accessory structures (e.g. Prostate), male secondary sex characteristics (facial hair growth of larynx)
Describe the female hormonal changes that occur during puberty
Oestrogen induces secondary ex characteristics (growth of pelvis, deposit of subcutaneous fat, maturation of internal reproductive organs, external genitalia)
Androgens release by adrenal glands increases growth of pubic hair, growth of bone, increased secretion from sabaceous glands
What initiates the first ovarian cycle?
LH surge. Usually not sufficient to cause ovulation during 1st cycle. Brain and endocrine system mature soon thereafter. Oestrogen levels increase due to growing follicles.
Describe the tanner classification system for pubertal development of girls
Breast B 1-5
Pubic hair PU 1-5
Axillary hair A 1-5
Menarche
Describe the tanner classification system for pubertal development of boys
Testicular volume over 4ml Te Penis enlargement G 1-5 Pubic hair PU 1-5 Axillary hair A 1-5 Spermarche
At what approximate speed is the pubital growth spurt?
Growth velocity is 2-3 times greater than prepupertal.
What is the normal age for the start of pubertal development in boys?
10 to 14
What is the normal age for the start of pubertal development in girls?
9 to 13
What is usually the 1st sign of puberty in boys?
G2 (testicular volume up to 4ml)
What is usually the 1st sign of puberty in girls?
B2
What is usually the growth velocity during puberty in boys?
10.3 cm/yr
Tanner 3-4
What is usually the growth velocity during puberty in girls?
9.0 cm/year
Tanner 2-3
What is the normal duration of puberty (in years) in boys?
3.2 +/- 1.8
Adult size of testes
What is the normal duration of puberty (in years) in girls?
2.4 +/- 1.1
Menarche
What is precocious puberty?
Defined as occurring younger than 2 SD before the average age.
What is the prevalence of precocious puberty?
1 in 5000 to 1 in 10,00
5 to 10 times more common in girls
At what age, in girls, would onset of puberty be considered to be precocious?
Less than 8 yrs
At what age, in boys, would onset of puberty be considered to be precocious?
Less than 9yrs
What causes precocious puberty?
Majority unknown cause.
Could be:
Gonadotrophin dependant (central) - hormone secreting tumour.
Gonadotrophin independent (neurological) early stimulation of central maturation, pineal tumours, meningitis
What might cause gonadotrophin dependant precocious puberty?
Tumours
Gonadotrophin secreting tumour (rare)
Gliomas, astrocytomas, harnartomas, pineal tumours, HCG secreting germ cell tumours
CNS trauma or injury (infection, radiation, surgery)
Hamartomas of the hypothalamus
Congenital disorders e.g. Hydrocephalus and arachnoid cysts
What is precocious pseudopuberty?
Appearance of secondary sexual characteristics due to an increased producing of female/male hormones. Occurs independently to HPG axis. Gonads mature without GnRH stimulation - levels of testosterone/oestrogen raised whilst LH and FSH are suppressed
What might cause precocious pseudopuberty?
Congenital adrenal hyperplasia
Testotoxicosis (or familial male precocious puberty) - autosomal dominant condition. Rapid physical growth, sexual maturation and sexually aggressive behaviour in first 2/3 yrs of life.
Exogenous oestrogen or androgen exposure (therapeutic or accidental)
Tumours:
HCG secreting tumours in liver
Choriocarcinomas of gonads, pineal gland, mediastinum (ovarian tumours may cause either masculinisation or feminisation. Testicular leydig-cell tumours may cause early virilisation in males)
Adrenal tumours (rare)
What tumours may cause precocious pseudo puberty?
HCG secreting tumours in liver Choriocarcinomas of gonads, pineal gland, mediastinum (ovarian tumours may cause either masculinisation or feminisation. Testicular leydig-cell tumours may cause early virilisation in males) Adrenal tumours (rare)
At what age would delayed puberty be declared if initial physical changes of puberty are not present by in girls?
13
Or primary amenorrhea by 15.5yrs
At what age would delayed puberty be declared if initial physical changes of puberty are not present by in boys?
14
How long should the interval between first signs of puberty and completion of genital growth/menarche be?
Less than 5yrs
What might cause gonadal failure? (Hypergonadotrophic hypogonadism)
Post malignancy chemo/radiotherapy/surgery
Polyglandular autoimmune syndromes
Hereditary e.g. Turner’s syndrome
What might cause gonadal deficiency?
Congenital hypogonadotrophic hypogonadism (+anosmia)
Hypothalamic/pituitary elisions (tumours, post radiotherapy)
Rare gene mutations inactivating FSH/LH at their receptors
What are the symptoms of menopause?
Itchy, twitchy, sweaty, sleepy, bloated, moody, forgetful…
What happens pre-menopause?
Changes in menstrual cycle, follicular phase shortens. Ovulation early or absent, less oestrogen secreted. LH and FSH levels rise (FSH moreso).
Reduced feedback, reduced fertility
At what age does menopause generally occur from?
Approx 40 yrs
What is menopause?
Cessation of menstrual cycles. Average age 49-50, but variable. No more follicles develop.
12 months of no menstruation.
What happens to the hormones in menopause?
Oestrogen levels fall dramatically, FSH and LH levels rise. (FSH dramatically, no inhibin)
What are hot flushes?
Vascular changes seen in menopause, affect cerca 80% to some degree. Transient rises in skin temp and flushing.
What might relieve hot flushes?
Oestrogen trestment
What occurs to the up uterus during menopause?
Regression of endometrium. Shrinkage of myometrium
What occurs to the female reproductive tract during menopause?
Thinning of cervix
Vagina rugae lost
Uterus - Regression of endometrium. Shrinkage of myometrium
What changes outside of the female reproductive tract occur in menopause?
Changes in skin.
Involution of some breast tissue
Changes in bladder, loss of pelvic tone (urinary incontinence)
Bone - reduced in mass by 2.5% per year henceforth
What changes occur to bone structure in menopause? Why?
Bone - reduced in mass by 2.5% per year henceforth
Reduced oestrogen enhances osteoclasts ability to absorb bone. Osteoporosis (greater in some than others). Fractures later in life, can be limited by oestrogen therapy
Describe hormone replacement therapy in treatment of menopause
Relieves symptoms of menopause. Can improve well being. Oestrogen given orally of topically by patch or gel. Can limit osteoporosis, current advice no longer recommended as 1st line treatment. Not advices for cardioprotection
Is there a male menopause?
No obvious event. Sperm production continues
What is the menstrual cycle?
Th interaction of the CNS, namely hypothalamus and pituitary and the ovaries, resulting in the cyclic and ordered sloughing of the uterine endometrial lining
What are the key hormones of the menstrual cycle?
GnRH gonadotrophin releasing hormone
FSH follicle stimulating hormone
LH luteinising hormone
Estradiol and progesterone
What is the proliferative phase of the menstrual cycle?
Begins at the onset of menses until ovulation taken place
What takes place during the proliferative phase of the menstrual cycle?
Folliculogenesis. A dominant follicle is selected from a pool of growing follicles that are destined to ovulate. Growth of follicles at this stage depends on pituitary hormones. Growth of follicle leads to production of estradiol from the layers of granulosa cells surrounding it. Estradiol is responsible for the proliferation of the endometrial lining of the uterus.
What does growth of follicle lead to?
Growth of follicle leads to production of estradiol from the layers of granulosa cells surrounding it. Estradiol is responsible for the proliferation of the endometrial lining of the uterus.
What does estradiol do?
Estradiol is responsible for the proliferation of the endometrial lining of the uterus.
When does ovulation occur?
At the peak of follicular growth, in response to LH surge
Approx what size are follicles prior to ovulation?
Over 20mm in average diameter
Describe the ovulation phase of the menstrual cycle
LH is released in a positive feedback mechanism from the anterior pituitary due to prolonged exposure to estradiol. For this positive feedback to take place, levels of estradiol above 200 pg/ml for approx 50h are necessary
What is required to initiate the positive feedback response of LH release in the LH surge?
For this positive feedback to take place, levels of estradiol above 200 pg/ml for approx 50h are necessary
By what mechanism is the oocyte released from the follicle?
Several proteolytic enzymes and prostaglandins are activated, leading to digestion of the follicle wall collagen
Describe what happens during the secretory phase of the menstrual cycle?
The remaining granulosa cells that are not released with the oocyte during the ovulation process enlarge and acquire lutein (carotenoids), which is yellow.
These granulosa cells are now called the corpus luteum and predominantly secrete progesterone. Peak progesterone production is noted 1 week later after ovulation takes place.
What does the lifespan of the corpus luteum depend on?
Continued LH support from the anterior pituitary, or, if a pregnancy occurs then HCG of pregnancy would maintain corpus luteum
What does the corpus luteum predominantly secrete?
Progesterone
What will happen to the corpus luteum if no pregnancy occurs?
Luteolysis occurs and the corpus luteum is converted to a white scar called the carpus albicans
What happens to the remaining granulosa cells that are not released in ovulation?
Enlarge and acquire lutein (carotenoids), which is yellow. Now called the corpus lutein, and predominantly secrete progesterone.
Approximately how long is a menstural cycle?
24-32 days
When might the menstrual cycle be longer?
After menarche
When might the menstrual cycle be shorter?
In pre menopause
When is regularity of the menstrual cycle generally best?
Between the ages of 20-40 yrs
What is the median blood lost per cycle?
37-43ml/cycle. Mostly in the first 48hrs
What is most important with regards to menstrual cycles?
Pattern/amount. What is normal.
What is menorrhagia?
Heavy periods
What might cause menorrhagia?
Abnormal clotting, pathology, fibroids, IUCD, medical disorders, cancer, progesterone contraception
List 5 types of uterine fibroids
Intracavitary, pedunculated, subserosal, submucosal, intramural
What is DUB
Dysfunctional uterine bleeding
What is dysfunctional uterine bleeding DUB?
60% heavy bleeding. No recognisable pelvic pathology, pregnancy or general bleeding disorder
What might cause irregular bleeding?
Hormonal contraceptives
Missed combined pills/missed progesterone only pill
Vomiting/diarrhoea whilst on the COCP
Certain prescription medicines or St Johns wort (a herbal remedy) whilst using the pill, patch, ring or implant
Irregular bleeding is common during the 1st 3 months of starting hormonal contraception, such as?…
COCP Progesterone only contraceptive pill Contraceptive patch (transdermal patch) Contraceptive implant or injection Intrauterine system IUS
What types of amenorrhoea are there?
Prepubertal, pregnancy, menopause, uterine/endometrial, ovarian, pituitary, hypothalamic
What is the possible impact of menstrual disorders?
Physical - tiredness, anaemia
Psychological - depression, irritability, mood swings, anxiety
Social - impact on ability to socialise, swim, perform sports
What makes up the linea terminalis?
The arcuate line, pectineal line and pubic crest
What type of pelvis is good for childbirth?
Gynecoid
Describe the features of a gynecoid pelvis
Round inlet Straight side walls Ischial spines not too prominent Well rounded greater sciatic notch Well curved sacrum Sub pubic arch over 90 degrees
What is the ‘true’ pelvis?
The lesser pelvis. Bony canal. Solid and immobile
What is the ‘false’ pelvis?
The greater pelvis. No obstetric relevance
What are the 4 pelvic planes?
Pelvic inlet
Plane of greatest diameter
Plane of least diameter
Pelvic outlet
How might you clinically assess the pelvic inlet?
Anteroposterior diameter
How might you clinically assess the mid pelvis?
Check for straight side walls. Bispinous diameter
How might you clinically assess the pelvic outlet?
Infrapubic angle. Distance between ischial tuberosities
Where is the obstetric conjugate measured from?
Measured from the sacral promontory to the midpoint of the pubic symphysis
Where do you measure the diagonal conjugate from?
Measured from the sacral promontory to the inferior border of the pubic symphisis
What are the ligaments of the pelvis?
Sacrospinous ligament
Sacrotuberous ligament
Describe a gynecoid pelvis
Circular pelvic inlet
80-85 degrees
Well rounded greater sciatic notch
Describe an android pelvis
Heart shaped inlet
Prominent projecting promontory
Prominent medically projecting ischial spines
50-60 degrees
What is the scrotum?
Cutaneous sac developed from labioscrotal folds. Contains the testes, epididymis and first part of the spermatic cord.
What is the scrotum developed from?
labioscrotal folds.
What does the scrotum contain?
Contains the testes, epididymis and first part of the spermatic cord.
What surrounds the testes?
Tunica vaginalis. Enclosed by tunica albuginea
Are the testes enclosed in peritoneum?
No
What organises the testes into lobules?
Fibrous septae
Describe the descent of the testes
Gonads develop within the mesonephric ridge. Descend through the abdomen. Testes cross the inguinal canal. Testes exit the anterio lateral abdominal wall
Describe the arterial supply to the testes
Direct branches from the abdominal aorta
Describe the venous drainage of the testes
Right - right testicular vein to the IVC
Left - left testicular vein to the left renal vein
What is the epididymis?
Connects the seminiferous tubules via efferent ductules and fete testes. Head, body and tail.
What is the spermatic cord?
Contains the structures running to and from the testes, neurovascular structures and duct system.
From the deep inguinal ring, lateral to inferior epigastric vessels, via the inguinal canal and superficial inguinal ring, to the posterior border of the testis.
Describe the course of the spermatic cord
From the deep inguinal ring, lateral to inferior epigastric vessels, via the inguinal canal and superficial inguinal ring, to the posterior border of the testis.
Describe the contents of the spermatic cord
Lymphatic Processes vaginalis Vas deferens Pampiniform plexus Genital branch of genitofemoral nerve 3 arteries - testicular, cremasteric, artery to vas deferens
Describe the coverings of the spermatic cord
External spermatic fascia (aponeurosis of external oblique)
Cremasteric muscle and fascia (internal oblique and transversalis)
Internal spermatic fascia (transversalis fascia)
What is hydrocoele?
Serous fluid in vaginalis
What is haematocoele?
Blood in tunica vaginalis
What is varicocoele?
Varicosities of pampiniform plexus
What is spermatocoele?
AKA epididymal cyst
Retention cyst within epididymis
What is epididymitis?
Inflammation of the epididymis
Why is transillumination important when analysing the scrotum?
Light passes through liquid but not solid
What is an indirect hernia?
Reopening of the processus vaginalis. Potential continuity between peritoneal cavity and the tunica vaginalis (between abdomen and scrotum). Via canal
What is testicular torsion?
Twisting normally occurs just above upper pole. Risks of necrosis of testis
Describe the innervation of the testis
Anterior surface - lumbar plexus
Posterior and inferior surfaces - sacral plexus
Describe the lymphatic drainage of the testis
Drains to paraaortic nodes
Describe the lymphatic drainage of the scrotum
Drains to superficial inguinal nodes
Describe the course of the ductus vas deferens
Ascends in spermatic cord. Traverses inguinal canal. Tracks around pelvic side wall. Passes between bladder and ureter. Forms dilated ampulla. Opens into ejaculatory duct.
Where does the seminal vesicle lie?
Between the bladder and the rectum
Is the seminal vesicle a storage site?
No
What forms the ejaculatory duct?
Duct of seminal vesicle combine with the vas deferens to form ejaculatory duct
Approx how much of ejaculate comes from diverticulum of vas deferens? (Seminal vesicle)
70-80%
What is the important anatomical relationship of the prostate base?
Neck of bladder
What is the important anatomical relationship of the prostate apex?
Urethral sphincter and deep perineal muscles
What is the important anatomical relationship of the prostate muscular anterior surface?
Urethral sphincter
What is the important anatomical relationship of the prostate posterior?
Ampulla of rectum
What is the important anatomical relationship of the prostate infero lateral surface
Levator ani
What is benign prostatic hyperplasia?
Increased sized middle lobule. Obstruction of internal urethral orifice.
What are the symptoms of benign prostatic hyperplasia?
Dysuria, nocturia, urgency
How might prostatic malignancies metastasise?
Via lymphatic route (internal iliac and sacral nodes) Venous routes (internal vertebral plexus to vertebrae and brain)
Describe the structure of the penis
Consists of a root, body and glands. Internal structure consists of a pair of corpora cavernosa dorsally, and a single corpus spongiosum ventrally
What arteries supply the penis?
Branches of internal pudendal arteries
Describe the blood supply to the male perineum
Internal pudendal artery is a branch of the anterior division of the internal iliac artery
What does bulbospongiosus do?
Helps expel last drops of urine, and maintain erection
What does ischiocavernosus do?
Compresses veins, therefore helping maintain erection
Describe the divisions of the male urethra
Pre prostatic, prostatic, membranous (pierces through peroneum), spongy
Which part of the male urethra pierces through the peroneum?
Membranous portion
What type of cells form the blood testis barrier ?
Sertoli cells. Also cells of germ cell lineage
What type of tumours are 90-95% of testicular neoplasms?
Germ cell tumours
How do seminiferous tubules converge on the rete testis?
Via the tubule recti
What type of cells form the exit duct system for male germ cells?
Simple cuboidal
What does the efferent duct of the male reproductive tract connect?
The rete testis with the head of the epididymis
What epithelium does the efferent duct of the male reproductive tract have?
Characteristic scalloped epithelium
How is sperm transported along the efferent duct of the male reproductive tract?
Combined ciliary action and myoid contraction
What is the epididymis?
Smooth muscle tube lined by pseudostratified epithelium. Characterised by the presence of stereocilia. Sperm maturation is completed (mobile)
What type of cells lines the epididymis?
Pseudostratified epithelium. Characterised by the presence of stereocilia
Describe the layers of the vas deferens
4 layers tube, epithelium and 3X smooth muscle
What is the function of the vas deferens?
Connects epididymis with ejaculatory duct. Smooth muscle contracts powerfully during ejaculation
What is the seminal vesicle?
Secretory epithelium, contributes 85% ejaculate volume. Smooth muscle layer. Sympathetic innervation enables discharge of contents into duct.
What proportion of ejaculate volume is from the seminal vesicle?
85%
What type of innervation enables discharge of seminal vesicle contents?
Sympathetic
What is the prostate?
Collection of 30-50 tubule-alveolar glands draining into prostatic urethra. Ejaculatory ducts merge with urethra within the prostate. Characteristic fibromuscular stroma.
Where does the ejaculatory duct merge with the urethra?
Within the prostate
In which zone does benign prostatic hyperplasia occur?
Transition zone
In which zone does adenocarcinoma of the male reproductive tract generally occur?
Peripheral zone
List the sequence of ovarian follicular development
Primordial, primary, pre-antral, early antral, mature, corpus luteum
What is a primordial follicle?
Small oocyte with flat follicular cells
What is a primary follicle?
Oocyte with maximum diameter with one or more layers of cuboidal granulosa cells. Zona pellucida develops.
Where does 90% of ovarian cancer arise?
Epithelium
What is stroma?
Theca and granulosa cells, may also give rise to tumours
What is the endometrium comprised of? (Layers)
Stratum basalis
Stratum functionalis, which is comprised of
Stratum spongiosum
Stratum compactum
Describe the histiological appearance of the uterus in the early proliferative phase of the menstrual cycle
Glands sparse, straight
Describe the histiological appearance of the uterus in the late proliferative phase of the menstrual cycle
Functionalis has doubled, glands now coiled
Describe the histiological appearance of the uterus in the early secretory phase of the menstrual cycle
Endometrium max thickness, very pronounced coiled glands
Describe the histiological appearance of the uterus in the late secretory phase of the menstrual cycle
Glands adopt characteristic ‘saw tooth’ appearance
Describe the histology of the cervix
Endocervical canal with mucus secreting, simple columnar epithelium. Ectocervix with stratified squamous non-keratinised epithelium. Squamocolumnar junction SCJ can be located at any point across the cervix
What is the transformation zone in the cervix? Why is it significant?
Adjacent to the SCJ (squamocolumnar junction). Absolute junction between one type of epithelium and another. Where the majority of neoplasms arise.
Describe the histology of the vagina
3 layered fibromuscular canal. Glycogen producing non keratinised squamous epithelium. Submucosa rich in elastin fibres and highly vascular. No glands.
Describe the histology of the breast
A single lactiferuos duct opens from each of multiple (15-20) lobes. Main duct branches repeatedly. Terminal ducts. Lobular unit, consisting of multiple acini.
Approx 70% breast malignancies are infiltrating ducts carcinoma
What’s the most common type of breast malignancy?
Approx 70% breast malignancies are infiltrating ducts carcinoma
Describe the appearance of inactive breast tissue
Limited development of duct alveolar system. Relatively dense fibrous interlobar tissue
Describe the appearance of lactating breast tissue
Highly developed with milk secretions in alveolar lumen. Interlobular tissue reduced to thin septa
Describe the descent of the female gonads
Gonads develop in the mesonephric ridge. Descend through abdomen, but stop in the pelvis
What is the arterial supply to the ovary?
Direct branches from the abdominal aorta
Describe the venous drainage of the right ovary
Right ovarian vein to the IVC
Describe the venous drainage of the left ovary
Left ovarian vein to left renal vein
What is the top of the uterus called? (Palpable in pregnancy)
Fundus
What is the anterior peritoneal pouch called?
Uterovesical pouch
What is the posterior peritoneal pouch called in the female?
Rectouterine pouch AKA pouch of Douglas
Posterior formix of the vagina
What is the posterior peritoneal pouch called in the male?
Rectovesical peritoneal recess
Describe the development of the peritoneal pouches
Paramesonephric ducts, a pair of ducts that are open cranially and connect to the urogenital sinus caudally. Persist in the absence of MIH. Fusion of the ducts in the midline creates a broad transverse fold draped by peritoneum.
What is the broad ligament?
Peritoneal fold in the female pelvis. Mesentery of the uterus, uterine tube and ovary.
What is the round ligament?
Attached to ovary and labium majus, travels through inguinal canal. Consequences for lymphatic drainage
What is the round ligament embryologically?
Gubernaculum
What is an anteverted uterus with respect to?
Vagina
What is an anteflexed uterus with respect to?
The cervix
What constitutes then uterine tube?
Abdominal ostium, fimbria, infundibulum, ampulla and isthmus
What is the function of the uterine tube?
To conduct the oocyte into the uterine cavity. Normally the site of fertilisation
Is the lining of the uterine tube similar to that of the uterine cavity?
No - consequences for ectopic implantation
How is the female peritoneal cavity open?
Via the ostium of the uterine tube
Describe the support of the pelvic viscera
Transverse cervical ligament - thickening at the base of broad ligament. Lateral stability of cervix. Uterosacral ligament opposes anterior pull of round ligament, assists in maintaining anteversion.
Describe the blood supply to the female internal genitalia
Ovarian artery - branches from abdominal aorta
Uterine artery - anterior division of internal iliac
Internal pudendal - anterior division of internal iliac
Describe the lymphatic drainage of the ovaries
Drains to paraaortic nodes
Describe the lymphatic drainage of the uterus
Fundus - to aortic nodes (and inguinal nodes)
Body - to external iliac nodes
Cervix - external and internal iliac nodes and sacral nodes
Where is the labia majora?
Enclosing the pudendal cleft
Where is the labia minora?
Enclosing the vestibule of the vagina (bulb of vestibule, clitoris)
What is enclosed in the vestibule?
Orifices of urethra, vagina, greater and lesser vestibular glands
What are the greater vestibular glands also called?
Bartholin glands (barthdinitis, bartholin gland cyst)
Describe the vagina orifice
Vagina orifice opens into the vestibule along with the external urethral orifice and the ducts of the greater and lesser vestibular glands.
Vaginal fornices - recesses if vagina around the cervix
What are Vaginal fornices?
recesses if vagina around the cervix
Describe the innervation of the vagina
Inferior 1/5 of vagina receives somatic innervation from pudendal nerve
Superior 4/5 of vagina and uterus receives innervation from uterovaginal plexus
Describe the pain afferents of the vagina
Vary depending on pelvic pain ripe thoracic lumbar spinal ganglia
S2 to S4 spinal ganglia
Describe the innervation of the perineum
Pudendal nerve, plus ilioinguinal nerve
Describe the course and distribution of the pudendal nerve
Exits pelvis via greater sciatic foramen. Enters perineum via lesser sciatic foramen. Travels through pudendal canal.
What is the pelvic floor?
Muscular and fibrous tissue diaphragm. Fills the lower part of the pelvic canal. Closes the abdominal cavity. Defines the upper border of the perineum. Supports the pelvic organs. Pierced by the urethra, vagina and rectum.
Describe the pelvic side wall
Ischium of pelvis, sacrospinous and sacrotuberous ligaments, obturator nerve and membrane, obturator internus. Piriform and coccygeus, branches of sacral plexus. Fascia (including tendineus), levator ani muscles. Internal iliac vessels and branches, ureters.
Describe the pelvic floor
Levator ani - puborectalis, pubococcygeus, iliocococcygeus.
What is attached to the pelvic side wall?
Ischial spine, arcus tendineus fascia pelvis, urogenital hiatus allows passage of urethra, vagina and rectum.
Describe the main blood vessels of the pelvis
Branches of posterior trunk of internal iliac artery (pudendal artery, vaginal artery, inferior rectal artery)
Describe the major nerves of the pelvis
Pudendal nerve S2,3,4 ‘keeps your guts off the floor’
What is the perineum?
Fibromuscular sheet which closes the pelvic outlet. Lower limit of perineal space. Perineal space continues with ischiorectal fossa. Perineal muscles. Perineal body.
What constitutes the perineum?
Urogenital diaphragm, transverse perineal muscles, ischiocavernosus, perineal body, bulbospongiosus
What is the perineal body?
Connective tissue mass in centre of perineum. Anchors the perineal muscles and rectum. Central fulcrum for pelvic support.
What does the pelvic floor do?
Supports the pelvic organs - retains uterus and bladder in correct positions
Contributes to continence - sphincter mechanism directly and indirectly
Contributes to the process of childbirth
Contributes to ‘truncate stability’
Describe some of the possible effects of childbirth on the woman’s anatomy
Stretch of pudendal nerve (neuropraxia and muscle weakness)
Stretch and damage of pelvic floor and perineal muscles (muscle weakness)
Stretch/rupture of ligaments support of muscles (ineffective muscle action)
Describe some consequences of the effects of childbirth on a women
Lack of support of pelvic organs - prolapse
Contributions to continence - incontinence
What other factors affect the effects of childbirth on a women
Age, menopause (atrophy of tissues after oestrogen withdrawal), obesity, chronic cough, intrinsic connective tissue laxity (defined conditions, constitutional)
What are the treatment options for urinary incontinece?
Pelvic floor muscle exercise
Surgery
Describe some continence procedures used to treat urinary incontinence
Increase support to sphincter mechanism and prevent descent of bladder neck (colposuspension, tension free vaginal tape). Effective. Side effects, voiding difficulty/retention, overactive bladder disease (obstruction)
Describe possible treatments for a vaginal prolapse
Remove prolapsed organs. Restore connective tissue supports. Maintain function. Side effects, recurrence, new incontinence, dysparenuria.
What is pelvic inflammatory disease PID?
The result of infection ascending from the endocervix, causing endometritis, salpingitis, parametritis, oophoritis, tube-ovarian abscess and/or pelvic peritonitis.
What is endometritis?
Inflammation and infection of the endometrium (lining of the uterus)
What is salpingitis?
Inflammation of Fallopian tube
Briefly outline the pathophysiology of pelvic inflammatory disease PID
Ascending infection from the endocervix and vagina. Infection causes inflammation, which causes damage. Therefore damaged tubal epithelium, adhesions form
List some complications of pelvic inflammatory disease PID
Ectopic pregnancy, infertility, chronic pelvic pain, fitz-hugh-curtis syndrome (RUQ pain and peri-hepatitis following chlamydia PID)
Briefly outline the aetiology (cause) of PID
Often polymicrobial. Sexually transmitted infections (c. Trachomatis, n. Gonorrhoea). Also gardnerella vaginalis, mycoplasma, anaerobes.
