Spermatogenesis & Male infertility Flashcards
What determines the male and female phenotypes ?
- Male phenotype depends on 22 homologous pairs of chromosomes + XY chromosomes (46 total) & andorgen production
- Female phenotype depends on 22 homologous pairs of chromosomes + XX chromosomes (46 total)
What is the sex determining region for male reproductive development ?
They Y chromosome
What does the reproductive tract in every fetus begin with before differentiating into male or female ?
A bipotential gonad & the wollfian & mullerian ducts
How does the Y chromsome result in development of the male internal reproductive tract ?
- It causes development of testis from the bipotential gonad (7th week onwards)
- Leydig cells secrete Testosterone (converted to dihydrotestosterone; DHT)
- Sertoli cells secrete Mullerian Inhibiting Factor
Testosterone and Mullerian Inhibiting Factor cause the development of the male internal genital tract
What is the effect of testosterone and mullerian inhibiting factor on the wollfian and mullerian ducts ?
- T: Wolffian ducts → reproductive tract (epididymis, vas deferens, seminal vesicles)
- MIF: Mullerian ducts degenerate
Without stimulus of male testicular hormones, fetus will develop female internal genital tract - T or F?
True
What happens to the wollfian and mullerian ducts during female internal reproductive tract development ?
There is no secretion of testosterone or mullerian inhibiting factor so:
- Wolffian ducts degenerate
- Mullerian ducts → reproductive tract (uterus, fallopian tubes, cervix, upper 1/3 vagina)
How does differentiation of the male external genitalia occur ?
Testosterone produced by the testis is converted into dihydrotestosterone causing the undifferentiated external genitalia to develop into male genitalia e.g. penis, scrotum
How does differentiation of the female external genitalia occur ?
There is absence of testosterone so the wollfian ducts degenerate & the undifferentiated external genitalia develop into female genitalia e.g. clitoris & labia
Go over this pic showing an overview of male & female reproductive tract development
Define what an androgen is
This is a male sex hormone - the main one being testosterone
Describe what androgen sensitivity syndrome is
This is when someone is genetically male (46 XY) but is resistant to andorgens, resulting in the physical traits of a women but the genetic make-up of a man
What type of inheritance is androgen sensitivity syndrome ?
X-linked recessive disorder
How does androgen sensitivity syndrome occur
- Patient has androgen resistance
- Testis develop but dont descend
- Androgen induction of wolffian duct does not occur, mullerian duct inhibition does occur (as mullerian inhibiting factor is not an androgen & testis is producing both T & MIF) ==> born with female external genitalia (as external genitalia under T control) but without a uterus & ovaries (internal genitalia under MIF control)
How does androgen sensitivity syndrome commonly present ?
At puberty with primary amenorrhoea & lack of pubic hair
Describe the descent of the testis
In utero testis develop in the abdo cavity & drop into the scrotal sac before birth (androgen-dependant)
Why is it important that the testis descend ?
Because the lower temp in the scrotal sac fascilitates spermatogenesis
What is the word used to describe undescended testis ?
Cyroptochidism (one or both testis)
What are the clinical implications of undescended testis ?
- Reduces sperm count, but if unilateral usually fertile
- Orcihdopexy (surgery to move undescended testicle into scrotum) should be performed < 14yrs old to minimise the risk of testicular germ cell cancer
- If testicle undescended as adult, consider orichdectomy as there is now a 6x increased risk of cancer
How can we change the temp of the tesits in the scrotal sac ?
Nervous refelexes trigger dartos muscle contraction into the scrotal sac to lower/raise the testis within the scrotal sac according to the external temperature
When should descent of the testis usually have occurred by ?
6-9months old
What are the 2 main functions of the testis ?
- Spermatogenesis in the seminiferous tubules
- Production of testosterone in leydig cells
List the different functions of sertoli cells
- Forms blood-testes barrier - this protects the sperm from antibody attack & ensures suitable fluid composition which allows later stages of sperm development
- Provide nutrients for the developing cells
- Phagocytosis - removes surplus cytoplasm & destroys defective cells
- Secrete seminiferous tubule fluid - used to carry cells to epididymis
- Secrete androgen binding globulin - so that testosterone concentration remains high in lumen which is essential for sperm production
- Secrete inhibin and activin hormones - regulates FSH secretion and controls spermatogenesis
What is the function of Gonadotrophin releasing hormone (GnRH)?
- Stimulates anterior pituitary to produce LH and FSH
- Under negative feedback control from testosterone
What are FSH & LH secreted by ?
The anterior pituitary gland
What role does LH & FSH play in control of spermatogenesis ?
LH - acts on Leydig cells - regulates testosterone secretion
FSH - acts on Sertoli cells to enhance spermatogenesis and regulates by negative feedback from inhibin
What are the effects of testosterone before, during and after birth ?
Before birth: masculinises reproductive tract and promotes descent of testes
Puberty: promotes puberty and male characteristics (growth and maturation male reproductive system)
Adult: controls spermatogenesis (has a -ve effect on hypothalamus & pituitary inhibiting GnRH, FSH & LH), secondary sexual characteristics (male body shape, deep voice, thickens skin), libido, penile erection,? aggressive behaviour)
What role does inhibin & activin play in spermatogenesis ?
- Secreted by Sertoli cell
- Feedback on FSH (inhibin inhibits and activin stimulates)
How long does spermatogenesis take and how long does the human body continue doing it ?
- Entire spermatogenic process takes 70 days
- Begins at puberty for and occurs for 60 years or more
Match the following accessory tissues to their function:
- Epididymis & vas deferens
- Seminal vesicles
- Prostate Gland
- Bulbourethral Glands
Secrete mucus to act as lubricant, Produce semen into ejaculatory duct, supply fructose, secrete prostaglandins (stimulates motility), secrete fibrinogen (clot precursor), Produces alkaline fluid (neutralizes vaginal acidity), produces clotting enzymes to clot semen within female, They are the exit route from testes to urethra, concentrate & store sperm, site for sperm maturation
- Epididymis & vas deferens - They are the exit route from testes to urethra, concentrate & store sperm, site for sperm maturation
- Seminal vesicles - Produce semen into ejaculatory duct, supply fructose, secrete prostaglandins (stimulates motility), secrete fibrinogen (clot precursor)
- Prostate Gland - Produces alkaline fluid (neutralizes vaginal acidity), produces clotting enzymes to clot semen within female
- Bulbourethral Glands - Secrete mucus to act as lubricant
Describe the route of sperm during ejaculation
Testes → epididymis → vas deferens → ejaculatory duct → urethra
Define what male infertility is
Infertility resulting from failure of the sperm to normally fertilise the egg. Usually associated with abnormalities in semen analysis
What are the causes of male infertility ?
IDIOPATHIC: most common cause (>50%)
OBSTRUCTIVE: vasectomy, cystic fibrosis (congenital absence of vas deferens), infection
NON-OBSTRUCTIVE:
- Congenital: Cryoptorchidism
- 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
List the endocrine causes of male infertility?
- Hypothalmic causes: idiopathic, tumours, Kallman’s syndrome, anorexia
- Pituitary tumours: acromegaly, cushings disease, hyperprolactinaemia
- Thyroid Disorders: hyper or hypothyriodism (decrease sexual function and increase prolactin)
- Diabetes (decrease sexual function and T)
- CAH: (increase T)
- Androgen insensitivity
- Steroid abuse (decrease T and LH, FSH)
List some of the drug causes which can cause male infertility ?
Just try learn the ones in bold
What are the features of non-obstructive infertility ?
Clinical Features:
- low testicular volume
- reduced secondary sexual characteristics
- vas deferens present
Endocrine features:
- High LH, FSH +/- low testosterone
What are the clinical features of Obstructive male infertility ?
Clinical Features:
- Normal testicular volume
- Normal secondary sexual characteristics
- Vas deferens may be absent
Endocrine features:
- Normal LH, FSH and testosterone
How should infertility be investigated initially ?
See as couple in designated infertility clinic & carry out:
History: infertility history, gynaecology, andrology, sexual history, social history, PMH, PSH, POH
Examination of female:
- BMI
- General examination, assessing body hair distribution, galactorrhoea
- Pelvic examination, assessing for uterine and ovarian abnormalities/tenderness/mobility
Examination of male:
- BMI
- General examination
- Genital examination, assessing size/position testes, penile abnormalities, presence vas deferens, presence varicoceles
What should be assessed during the exammination of a male with infertility ?
General examination:
- including secondary sexual characteristics, presence of gynaecomastia
Genital examination:
- testicular volume
- presence of vas deferens and epididymis
- penis (urethral orifice)
- presence of any varicocele/other scrotal swelling
What is the normal adult testicular volume and how is it assessed ?
- adults:12-25mls
- If below 5ml unlikely to be fertile, measured using orichdometer
What are the main parameters assessed during semen analysis ?
- Volume
- Density - numbers of sperm (concentration)
- Motility
- Progressive motility
- Morphology
What is the first investigation which should be done for specifically investigating male infertility ?
1st line = Semen analysis: twice over 6 weeks apart
What are the normal semen parameters ?
If abnormal semen analysis is reported what should then be done to investigate male infertility ?
Endocrine profile:
- LH and FSH
- Testosterone
- Prolactin
- Thyroid function
If severely abnormal semen analysis/ azoospermic what should be done to further investigate male infertility ?
- Endocrine profile (as in abnormal semen)
- Chromosome analysis and Y chromosome microdeletions
- Screen for CF
- Testicular biopsy
If abnormality on genital examination is detected when exammining someone with male infertility what additional investigation should then be done for them?
Scrotal U/S
What is the general advice given to help treat male infertility ?
- Frequency sexual intercourse: 2-3 X per week
- Avoid lubricants that are toxic to sperm
- Alcohol: < 5 units per week
- Smoking: associated decrease semen quality and decreased health
- Caffeine: nil evidence
- BMI: < 30 likely to improve fertility and health
- Avoid tight fitting underwear and prolonged hot baths/sauna may improve
- Certain occupations: overheating/exposure to chemicals
- Complementary therapies and non-prescription drugs
- Possible benefits of anti-oxidants (vitamin C or zinc)
What is the treatment of male infertility ?
- Treat any specific cause e.g. reversal of vasectomy if vasectomy, carbegoline if hyperprolactinamia
- Intracytoplasmic sperm injection (ICSI: may require surgical sperm aspiration)
- Donor Insemination (DI)
Go over these specific treatments for male infertility:
- Reversal of vasectomy: Success rate - 75% if you have your vasectomy reversed within 3 years
- Endocrine conditions e.g. cabergoline for hyperprolactinemia.
- Anejaculation e.g. psychosexual treatment.
- Chronic disorders e.g. renal failure.
- Medications e.g. steroids, immunotherapy.
