Spermatogenesis and Male Infertility Flashcards
when do primordial germ cells migrate to gonadal ridge?
week 5-6
what does Y chromosome cause?
development of testis at week 7
leydig cells secrete testosterone (will become DHT)
sertoli cells secrete mullerian inhibiting factor
ducts in males?
wolffian = becomes reproductive tract (epididymis, vas defrens, seminal vesicles)
mullerian duct = degenerates
ducts in females?
opposite
what does DHT stimulate?
development of male external genitalia
female genitalia develops in its absence
when can gender be differentiated on a scan?
week 16
starts to differentiate at wek 9
what is androgen insensitivity syndrome?
X linked congenital insensitivity to androgens
features of androgen insensitivity syndrome?
testes develop but dont descend
androgen induction of wolffian duct does not occur and mullerian inhibition does occur
causes phenotypically female external genitalia but without uterus or ovaries and a short vagina
often presents are puberty with primary amenorrhoea and lack of pubic hair
cells of the smeiniferous tubules?
sertoli cells
which cells produce sperm?
seroli sperm
descent of testes in utero?
testes develop in abdomen on foetus
descend into scrotal sac before birth (androgen dependent)
- etsticukar artery is branch of aorta
- veins in similar path (L testicular vein joins L renal vein, R drains straight into IVC)
- lymphatic drainage to abdomen
why must the testes descend?
need lower temp for spermatogenesis
what muscle controls lifting/descent of testes?
dartos muscle
what is cryptorchidism?
undescended testes
individual has reached adolescence/adulthood and testes have not descended
(usually descend by 6-9 months)
implications of chryptorchidism?
affects spermatogenesis (low sperm output)
germ cell cancer risk
- orchidopexy before age 14 can reduce risk
- or orchidectomy if adult
what does the urethra pass through in the penis?
corpus spongiosum
what causes an erection?
blood engorging in corpus cavernosum and corpus spongiosum
what hormone drives sertoli function and therefore sperm production?
FSH
where is genetic info held in sperm?
head
what else is contained within the sperm cell?
acrosome covers head (contains enzymes for penetrating ovum)
mitochondria in midpiece
6 functions of sertoli cells?
form blood-testes barrier (protects sperm from antibody attack)
provide nutrients for developing cells
phagocytosis (surplus cytoplasm and defective cells)
secrete seminiferous tubule fluid (carries cells to epididymis)
secrete androgen binding globulin (binds to testosterone to maintain high levels)
secrete inhibin and activin hormones (regulates FSH and controls spermatogenesis)
what does LH affect?
leydig cells
function of inhibin?
decreases secretion of FSH
FSH stimulates spermatogenesis so therefore causes low sperm
describe gonadotrophin releasing hormone?
decapeptide released from hypothalamus in bursts every 2-3 hours
stimulates anterior pituitary to produce LH and FSH
under negative feedback control from testosterone
what are gonadotrophins?
glycoproteins secreted by anterior pituitary
LH - acts on leydig cells to regulate testosterone
FSH - acts on sertoli cells to enhance spermatogenesis, regulates by negative feedback from inhibin
what produces testosterone?
leydig cells
what type of hormone is testosterone?
steroid derived from choelsterol
effects of testosterone?
negative feedback on anterior pituitary
before birth:
- masculine reproductive tract and promotes descent of testes
puberty:
- promotes puberty and male characteristics (growth and maturation male reproductive system)
adult:
- controls spermatogenesis, secondary sexual characteristics, libido, penile erection, aggressive behaviour
what are inhibin and activin?
peptides secreted by sertoli cells
feedback on FSH
- inhibin inhibits and activin stimulates
what happens to spermatozoa after ejaculation?
liquefied by enzymes from prostate gland
capacitation:
- series of biochemical cellular events before fertilization (hyperactivated motility, ability to bind to ZP and AR of egg)
chemoattraction to oocyte
penetration of cumulus complex
acrosome reaction/zona binding
fusion with oocyte membrane and fertilization
where does fertilization occur?
ampulla of fallopian tube
function of epididymis and vas deferens?
exit route from testes to urethra, concentrate and store sperm, site for sperm maturation
function of seminal veisicles?
produce semen into ejaculatory duct, supply fructose, secrete prostaglandins (stimulate motility) and secrete fibrinogen (clos precursor)
function of prostate?
produces alkaline fluid which neutralizes vaginal acidity
produces clotting enzymes to clot semen within female
function of bulbourethral glands?
secrete mucous to act as lubricant
general function of accessory glands?
secrete semen to suspend and sustain sperm
route of sperm?
testes > epididymis > vas deferens > ejaculatory duct > urethra
what causes erection?
blood fills corpora cavernosa (under parasympathetic control)
what causes emission?
contraction accessory sex glands and was deferens so semen expelled to urethra
what causes ejaculation?
contraction of smooth muscles of urethra and erectile muscles (sympathetic control)
definition of male infertility?
infertility resulting from failure of the sperm to normally fertilise the egg
usually associated with abnormalities in semen analysis
most common cause of male infertility?
idiopathic
obstructive causes of male infertility?
CF
vasectomy
infection
non-obstructive causes of male infertility?
congenital (e.g cryptorchadism) infection (e.g mumps) iatrogenic (chemo) pathology (testicular tumour) genetic (chromosomal e.g kleinfelter's) specific semen abnormality (e.g globozoospermia) systemic disorder endocrine
endocrine causes of male nfertility?
hypothalamus (idiopathic, tumour, kallman’s, anorexia)
pituitary tumours (acromegaly, cushings, hyperprolactinaemia)
thyroid (hyper/hypo)
diabetes
CAH (increases testosterone)
androgen insensitivity
steroid abuse (decerases testosterone and LH/FSH)
questions to determine testosterone levels?
feeling tired
needing to shave less
loss of libido
loss of early morning erection
examination in male infertility?
general (look for 2ndary sexual characteristics and gynaecomastia etc)
genital
- testicle volume
- presence of vas deferens and epididymis
- penis and urethral orifice
- presence of any variocele/other scrotal swelling
normal testicular volume?
pre-puberty = 1-3 mls
adult = 12-25 mls
unlikely to be fertile if under 5ml
how is testicular volume measured?
orchidometer
what is measured in semen analysis?
volume density (numbers of sperm) motility (how many moving) progression (how they move) morphology
what factors can influence result of semen analysis?
completeness of sample
period of abstinence (must be at least 2 days but no more than 7)
condition during transport (e.g too cold)
time between production and assessment (must be <1 hr)
natural variants between samples
health of man 3 months before production
further assessment in male infertility?
repeat semen analysis after 6 weeks
endocrine profile (LH, FSH, testosterone, PRL, TSH)
chromosome analysis
CF screen
depending on results - testicular biopsy, scrotal scan
clinical features of obstructive male infertility?
normal testicular volume
normal 2ndary sexual characteristics
vas deferens may be absent
normal LH, FSH and testosterone
clinical features of non-obstructive male infertility?
low testicular volume
reduced 2ndary sexual characteristics
vsa deferens present
high LH, FSH +/- low testosterone
general advice in male infertility?
frequent intercourse (2-3 times per week and avoid toxic lubricants)
<4 units alcohol per week
stop smoking
BMI <30
avoid tight fitting underwear and prolonged heat/hot water exposure
certain occupations (exposure to heat/chemicals etc)
complementary therapies and possible benefits of anti-oxidants etc
treatment of specific disorders in male infertility?
reversal of vasectomy (works best if done within 3 years and more worth it if female is young) endocrine (e.g cabergoline for hyperprolactinaemia) anejaculation conditions (e.g psychosexual treatment) chronic disorders (e.g renal failure) medications (steroids, immunotherapy etc)
IVF vs ICSI?
IVF = normal sperm used ICSI = sperm is abnormal so injected manually into the egg
methods of sperm retrieval?
PESA
TESA
testicular biopsy
normal testicular volume?
12-25mls
indications for donor sperm insemination?
azzospermia very low count failed ISCI genetic conditions infective conditions
