Spermatogenesis and Male Infertility Flashcards
What do the fetal testes secrete?
Testosterone
Mullerian inhibiting factors
What are the two primitive genital tracts?
Wolffian and Mullerian ducts
Where do the testes develop from?
Y chromosome has sex determining region: testes develop from bipotential gonad
What do testosterone and mullerian inhibiting factors cause the development of?
Male internal genital tract
What do the Wolffian and Mullerian ducts become?
Reproductive tract in males, Mullerian degenerates in males
Vice versa in females
What is the main hormone that causes the differentiation of external genitalia?
Dihydrotestosterone (present in males, absent in females)
What happens in androgen insensitivity syndrome (testicular feminisation)?
Congenital insensitivity to androgens
Testis develop but do not descend
Androgen induction of Wolffian does not occur, Mullerian inhibition does: phenotypically external female genitalia with absence of uterus and ovaries with short vagina
What are the genetics of androgen insensitivity syndrome?
X-linked recessive
Male karyotype: 46XY
Nervous reflex trigger what in scrotal sac to lower/raise testes according to external temperature?
Dartos muscle contraction
What is cryptorchidism?
Undescended testes
What are the clinical features of cryptorchidism?
Adulthood with undescended testes
Reduced sperm count, usually fertile if unilateral
What should be done to males <14yo with cryptorchidism to minimise the risk of testicular germ cell cancer?
Orchidopexy
What should be done in adults with undescended testes?
Orchidectomy
What is the function of the testes?
Spermatogenesis (seminiferous tubules) Testosterone production (Leydig cells)
What is a spermatozoon?
Single sperm
Acrosome contains enzymes for penetrating ovum
What are the roles of the Sertoli cells?
Form a blood testes barrier: protects from antibodies, provides suitable fluid composition
Provide nutrients
Phagocytosis: remove surplus cytoplasm and destroy defective cells
Secrete seminiferous tubule fluid: used to carry cells to epididymis
Secrete androgen binding globulin: binds testosterone to keep concentration high in lumen, essential for sperm production
Secrete inhibin/activing hormones: regulates FSH secretion and controls spermatogenesis
What does FSH stimulate in males?
Spermatogenesis together with testosterone
What does LH stimulate in males?
Testosterone secretion
What does testosterone decrease in males?
Release of GnRH and LH
What does dihydrotestosterone cause in males?
Enlargement of male sex organs
Secondary sexual characteristics
Anabolism
What is GnRH?
A decapeptide
When is GnRH released?
From hypothalamus in bursts every 2-3hours (begins 8-12yo)
What does GnRH do?
Stimulates anterior pituitary to produce LH and FSH
Under -ve feedback control from testosterone
What are LH and FSH?
Glycoproteins released from anterior pituitary
What does LH act on?
Leydig cells-regulate testosterone secretion
What does FSH act on?
Sertoli cells to enhance spermatogenesis
Regulates by -ve feedback from inhibin
Is LH/FSH production cyclical?
Not in males
What is testosterone?
Steroid hormone derived from cholesterol
Where is testosterone secreted?
Into blood and seminiferous tubules
What does testosterone produce -ve feedback on?
Hypothalamus and pituitary gland
What are testosterones effects before birth?
Masculinises reproductive tract and promotes descent of testes
What are testosterones effects at puberty?
Promotes puberty and male characteristics (grown and maturation male reproductive systems)
What are testosterones effects as an adult?
Controls spermatogenesis Secondary sexual characteristics (male body shape deep voice, thickens skin) Libido Erection Aggressive behaviour
What are inhibin and activin?
Peptides
What are inhibin and activin secreted by?
Sertoli cells
What do inhibin and activin provide feedback on?
FSH: inhibin inhibits and activin stimulates
What happens to spermatozoa after ejaculation?
Liquified
Capacitation: biochem and electrical events before fertilisation (hyperactived mobility, ability to bind)
Chemoattraction to oocyte and bind to zona pellucida
Acrosome reaction
Hyperactivated mobility
Penetration and fusion with membrane
Zonal reaction
What is the function of the epididymis and vas deferens?
Exit route from testes to urethra, concentrate & store sperm, site for sperm maturation
What is the function of the seminal vesicles?
Produce sperm into ejaculatory duct Supply fructose Secrete prostaglandins (stimulate motility) Secrete fibrinogen (clot precursor)
What is the function of the prostate gland?
Produces alkaline fluid (neutralises vaginal acidity)
Produces clotting enzymes to clot semen within female
What is the function of the bulbourethral glands?
Secretes mucus to act as lubricant
What is filled with blood during an erection?
Corpora cavernosa
What is emission?
Contraction of accessory sex glands and vas deferens so semen expelled to urethra
What occurs in ejaculation?
Contraction of smooth muscles of urethra and erectile muscles (Sympa control)
What is male infertility?
Infertility resulting from failure of the sperm to normally fertilise egg
Usually associated with abnormalities in semen analysis
What is the most common cause of male infertility?
Idiopathic
What are some obstructive causes of male infertility?
CF
Vasectomy
Infection
What are some non-obstructive causes of male infertility?
Congenital: Cryoptorchadism Infection: mumps orchitis Iatrogenic: chemotherapy/radiotherapy Pathological: testicular tumour Genetic: chromosomal (Klinefelter’s syndrome, microdeletions of Y chromosome, Robertsonian translocation) Specific semen abnormality e.g. globozoospermia Systemic disorder Endocrine
What pituitary causes exist for male infertility?
Acromegaly
Cushings disease
Hyperprolactinaemia (decrease LH/FSH/test.)
What are some hypothalamic causes of male infertility?
Idiopathic
Tumours
Kallman’s syndrome
Anorexia (decrease LH/FSH/test.)
What are some thyroid causes of male infertility?
Hyper/hypothyroidism (decrease sexual function and increase PRL)
How does diabetes cause male infertility?
Decrease sexual function and decrease test.
How does CAH cause male infertility?
Increase test.
How does androgen insensitivity cause male infertility?
Normal or raised LH and test.
How does steroid abuse cause male infertility?
Decrease LH/FSH/test.
What is particular about examination of male infertility?
Genital exam: testicular volume, presence of vas deferens and epididymis, penis (urethral orifice), presense of any varicocele/other scrotal swelling
What is the normal testicular volume?
Pre puberty: 1-3mls
Adult: 12-25mls
If below 5ml likely infertile
What is assessed in semen analysis?
Volume Density Motility (proportion moving) Progression (how well they move) Morphology
Beyond normal consultation and semen analysis, what further assessments can be carried out in male infertility?
Repeat semen analysis 6wks later Endocrine profile Chromosome analysis CF screening Biopsy, scrotal scan
In an obstructive diagnosis of male infertility, what are the clinical and endocrine features?
Normal volume, secondary sexual characteristics
Vas deferens may be absent
Normal LH/FSH/test.
In a non-obstructive diagnosis of male infertility, what are the clinical and endocrine features?
Low volume, reduced secondary sexual characteristics
Vas deferens present
High LH/FSH and low testosterone
How can male infertility be treated through lifestyle changes?
Sex 2-3x/week, avoid toxic lubricants
Alcohol: <4 units/day
Smoking: stop/decrease
BMI: <30
Avoid tight underwear/prolonged baths and saunas
Occupation: overheating, chemical exposure
Complementary therapies and non-prescription drugs
Benefits of anti-oxidants
What is IUI indicated?
Mildly reduced sperm count
What is the procedure in IUI and pregnancy rate?
Semen sample prepared to produce concentrated sample
Inseminated into uterine cavity around ovulation
15%
What is intracytoplasmic sperm injection indicated?
Very low sperm count
What is the procedure and pregnancy rate in ICSI?
Sperm injected into stripped oocyte obtained during IVF
30%
When is surgical sperm aspiration indicated?
Azoospermia
What is the procedure of surgical sperm aspiration, and the success rate at obtaining sperm?
Sperm aspirated surgically (diagnostic produce or at time of oocyte recovery)
95% in obstructed, 50% in non-obstructed
When is donor sperm insemination indicated?
Azoospermia or very low sperm count
Genetic or infective conditions
What is the procedure for donor sperm insemination?
Sperm donors (altruistic and not anonymous) matched for recipient characteristics and screened for conditions
Sperm quarantined by cryopreservation and rescreened
Prepared thawed sample inserted IU at ovulation
What is the pregnancy rate in donor sperm insemination?
15%
