Male Reproductive Physiology Flashcards
Make up of male X and Y chromosome
(what are PAR, SRY and MSY)
Sex determining region on Y chromosome (SRY)
Male specific region on Y chromosome (MSY) - encodes genes necessary for spermatogenesis
Pseudoautosomal region (PAR) - areas of homology w/ e X chromosome
what kinda gonad is there early in development?
factors that prompt male gonad development (sorry socks); factors that prompt female gonad development (2 fox’s wnt 4 a feast)
Bipotential gonad
+SRY; SOX9 = male
(no SRY) FOXL2, WNT4, FST = female
SRY codes for __ __ factor, which does what?
downstream genes activated by SRY promote development of __ and __ cells, and __ tubules
T/F: SRY is expressed over a wide developmental window and is expressed kinda everywhere
Codes for testis determining factor (TDF); initiates a cascade of gene expression
Leydig cells, Sertoli cells, and spermatogenic tubules
Falsehood: SRY only expressed around 6 weeks of gestation (very narrow window); and almost exclusively in gonads
Gonads develop from 3 sources, namely __, __, and ___
The ___ proliferates to form the genital ridge
___ originate outside the body in a proliferation zone of the embryonic yok sac, and migrate into the body along the urogenital sinus into the genital ridges
the mesothelium, the underlying mesenchyme, and the primordial germ cells
Gonad differentiation (internal UG tract)
what happens to the undifferentiated gonad in the presence of AMH and testosterone? (what’s the function of AMH?)
what happens when there’s no male sex hormones?
In males, the gonads become testes, the Wolffian ducts give rise to the epidiymides, vasa deferentia, seminal vesicles and ejaculatory ducts and the Mullerian ducts (i.e.the female system) regress
Anti-Mullerian hormone (AMH)
In females, the gonads become ovaries, the Mullerian ducts give rise to the fallopian tubes, uterus, and upper vagina and the Wolffian ducts persist in vestigial form
External genitalia differentiation:
what do the following become in males vs females:
genital tubercle, folds, swelling
In females, the genital tubercle becomes the clitoris, the genital swellings become the labia majora, and the genital folds become the labia minora
In males the genital tubercle becomes the glans penis, the genital swellings fuse to become the scrotum, and the genital folds elongate and fuse to form the shaft of the penis and the penile urethra, which terminates in the glans penis
process of testicular descent
Initial phase: the primitive gonad is located near the kidney, held by the cranial suspensory ligament (CSL) and the gubernaculum testis.
Transabdominal descent: androgen-mediated dissolution of the CSL and insulin like factor 3 (INSL3) mediated swelling of the gubernaculum
The testis is pulled into the scrotum by the gubernaculum; which tethers the testes and the inguinal canal; shrinks like a string
Inguino-scrotal migration: the testis passes through the inguinal canal into the scrotum, this phase is androgen-dependent
complications from testicular descent; describe them
(hint: the docs were repairing this when you shadowed in surgery; fluid in the string, the string being open)
- Inguinal hernia: piece of peritoneum gets into the inguinal canal
- Complete inguinal hernia: a whole loop of bowel gets into the canal
- Hydrocele of cord: processus vaginalis didn’t completely dissolve and fluid collects there
- Communicating hydrocele: processus vaginalis is actually open, so fluid is coming into the scrotum itself
Basic male genitalia anatomy (just memorize it)
Testis anatomy (what are the parts and describe the path that sperm travel)
- Collection of very long tubules packed tightly into lobules
- The tubules dump into the rete testis (Latin for sewer)
- Then into the epididymis, take long, winding journey to allow for maturation process
- Then into vas deferens and out of the body
Overview of spermatogenesis
(what’s the order of sperm development;
where is this taking place;
which cells are within this place and are “nursing” the growing sperm?
which cells are on the outside, producing androgens?)
spermatogonium >> primary spermatocyte >> secondary spermatocyte >> spermatid
Within the seminiferous tubules
Sertoli cells
Leydig cells are outside the seminiferous tubule and are the source of androgens
Leydig cells
…also called what?
where are they? they have receptors for who?
what do they do?
Also called interstitial cells
Located between the seminiferous tubules
Have receptors for LH, not FSH
Make testosterone
Sertoli cells
…also called what?
where are they? they have receptors for who?
what do they do?
Nurse cells
Make anti-Mullerian hormone
- Aromotize testosterone to estrogens
- Form blood-testis barrier; support germ cells
- Produce androgen binding protein, inhibin, seminal fluid
Overview of HPG axis (draw it, explain it)
(include which cells LH and FSH act on; what they secrete; the feedback pathway)
How is testosterone needed for sperm maturation when sertoli cells don’t have LH receptors?
-GnRH released by hypothalamus stimulates the synthesis and release of the gonadotropins FSH and LH by the pituitary
– in the testis, LH stimulates testosterone production (arrows by the Leydig cells
-Testosterone has an indirect local effect on spearmatogeneesis by binding to its receptors in the in the Sertoli cell nuclei
– in the testis, FSH stimulates inhibin production by the Sertoli cells (black arrowheads), which has a negative feedback on the pituitary release of FSH
Steriodogenesis pathway (how do we get to testosterone from DHEA? what’sDHT? where are these 2 made?)
Between testo and dht, who has the stronger binding affinity for the testo receptor?
Among Testo, androstenedione, estradiol and cortisol, which plasma protein is each mostly bound to?
-Androstenedione to testosterone by 17 beta hydroxy-dehydrogenase
DHT
Testo: mostly SHBG, some albumin, little free
Andro: mostly Albumin, little SHBG, some free
Estradiol: mostly Albumin, some SHBG, little free
Cortisol: mostly CBG, little albumin, little free
Testis and peripheral tissues
Things increasing measured SHBG
(when you’re an old alcoholic man, your thyroid gets hyper coz you’re off your convulsion meds; then 2 more)
Increased SHBG
Aging
Cirrhosis
Hyperthyroidism
Anticonvulsants
Estrogens
HIV infection
Things decreasing SHBG
(fat people’s kidney’s waste a bunch of proteins and their thyroid is small; Andrew’s made progress with his diabetes)
Decreased SHBG
Obesity
Nephrotic syndrome
Hypothyroidism
Glucocorticoids
Androgens
Progestins
Diabetes Mellitus
Androgren receptor domains
how does the receptor get activated/what’s the downstream effect
Receptor has N terminal domain; double helix binding domain; and ligand binding domain
See diagram
Functions of androgen in males
Differentiation of internal and external male genitalia
Stimulates bone growth
Initiation and maintenance of spermatogenesis
Stimulate and maintain binding proteins and secretory fluids
Behavior
What’s testo secretion going to look like over a lifespan? (see graph below)
Spikes of testo in fetal and neo-natal period; there’s a dormant phase for a while until puberty hits
1st signs (there’s 2 of them) of pubertal development?
Tanner staging for those 2 (hint: 1-5, 1 is pre-puberty, 5 is adult)
Stage 1: pre-pubertal testicular size <2.5mm in length and volume <3mL. Scrotum is thick and rugated
Stage 2: (puberty) enlargement of the testes and scrotum w/ thinning of the skin of the scrotum. No penile enlargement (4cc or larger; 2.5 mm +)
Stage 3: some penile enlargement in length. Cont enlargement of the testes and scrotum
Stage 4: lengthening and increased diameter of the penis, enlargement of the glans, cont incr in the scrotum and testes
Stage 5: adult size
Tanner staging for pubic hair growth (aka ___?)
Stage 1: nothing
Stage 2: fine sparse hair at the base of the penis
Stage 3: increased hair, darker and more curly. Seen from down the hallway
Stage 4: spread outward and more dense
Stage 5: adult pattern w/ spread of pubic hair onto the thighs
Explain the graph below
why are dudes generally taller than girls?
males are taller than females because they have their growth spurt approx 2 years later, so 2 additional year of pre-pubertal growth, they have a higher ht velocity so they grow faster, and the growth spurt is of longer duration
factors regulating timing of puberty
Neural signals
Nutrition
Environmental factors
Genetic factors
what happens to LH/FSH
what 2 other “tin” hormones are involved in puberty timing? (kiss the leps!)
what would be the effect of giving a GnRH agonist?
impact of obesity in puberty timing
- Transient appearance of circadian rhythm in LH/FSH secretion (elevated at night)
- Leptin and Kisspeptin
- Inhibit the pulsatile GnRH secretion, which is critical for growth, so you can actually slow down puberty
Obesity ass’d w/ earlier puberty in girls (that explains why everything happened earlier for me!! I was a big kid!!)
Roles of Leptin and kisspeptin
how is the timing of puberty related to kisspeptin?
how are steroids involved?
surge of leptin occurs just before puberty
- Leptin acts on hypothalamus, pituitary gland, gonads, adrenal gland, and epiphyseal growth plates
- Kisspeptin is synthesized in hypothalamus
- Kisspeptin neurons synapse directly on GnRH neurons
Kisspeptin has to be released during that dormant phase of testosterone for puberty to ensue
•Steroids act on neurons in the hypothalamus (not GnRH neurons)
precocious puberty
cause
difference between central and GnRH independent
Cause: •Early loss of HPG axis inhibition
GnRH dependent (central):
Idiopathic (70-90% in girls)
Pathologic in 50% of boys (hypothalamic harmatoma most common)
CNS insults (meningitis, trauma, tumors, hydrocephalus)
Gain of function mutation in kisspeptin/kesspeptin receptor (not so common)
GnRH independent
- Secretion of excess sex hormones independent of HPG axis (gonad, adrenal, exogenous, ectopic)
- Can cause secondary activation of HPG axis
Delayed puberty definition
causes
diff between primary and secondary hypogonadism
No testicular enlargement by age 14 years
Constitutional delay of growth and development
Primary hypogonadism: High LH/FSH
- Gonadal dysgenesis (isolated, Klinefelter’s syndrome)
- Gonadal failure (chemo, radiation, torsion, autoimmune)
Secondary hypogonadism: Low or “inappropriately normal” LH/FSH
Functional impairment of GnRH secretion (malnutrition; hypopituitarism)
Genetic: Kallmann’s syndrome, Prader-Willi
Idiopathic
Spermatogenesis requires __ and has to occur at __ temps than body temp
Define the following in terms of spermatogenesis
Spermatocytogenesis
Meiosis
Spermiogenesis
Spermiation
Androgens; colder (2 degrees lower)
Spermatocytogenesis = proliferation of spermatagonia by mitosis
Meiosis = formation of haploid spermatids
Spermiogenesis = maturation of spermatids into spermatozoa
Spermiation = release of spermatozoa from the Sertoli cells into the lumen of the seminiferous tubules
Spermiogenesis
Formation of acrosome at the anterior pole
Movement of centrioles to the posterior pole for tail development
Mitochondria concentrate in the middle, excess cytoplasm starts beiing shed; formation of acrosome cap
Repositioning of the developing spermatozoa to allow for flagellum development and release from Sertoli cells
Spermiation
__ stimulates the ___, which activates plasmin, needed for spermiation.
Release of spermatozoa from luminal surface of Sertoli cells
FSH
plasminogen activator
T/F: sperm secreted from Sertoli cells is fully capable of fertilizing an ovum by the time its released. (if false, what are the extra steps before the sperm are ready to fertilize an ovum?)
Typical ejaculate volume is ___, contains 80-120 millions sperm
T/F: Sperm is the major component of semen.
What are the other components? from seminiferous tubules, prostate, seminal vesicles, and bulbourethral glands
3 functions of semen (why does it have the secretions that it does?) (hint: the vagina is acidic and it transports prostaglandins to stop capacitating)
Falsehood. Sperm require additional 10-14 days to mature in epididymis; plus additional time in female reproductive tract (about 7 hrs)
Secretions from seminiferous tubules, prostate, seminal vesicles, and bulbourethral glands
Protects against vaginal acidity
Prostaglandins may promote transport
Prevents capacitation prior to fertilization
categories of semen analysis (characteristics of each)
Risk factors for abnormal semen analysis
sperm count, morphology and mobility
Higher sperm count ass’d with better fertility
Abnormal sperm will have a harder time fertilizing
Sperm motility – forward motility important
Contact w/ herbicides or insecticides
Exposure to DDT/DDE (antimalarial compounds) in endemic malaria areas
Maternal smoking
Basically any other exposure that may affect sperm (working with chemicals and bad fumes etc)
Acrosome definition
2 enzymes in the acrosome that carry out the acrosome reaction
Basically a bag of enzymes; aids w/ sperm entry into the ovum
Acrosin and hyaluronidase enzymes breakdown factors that are holding the cumulus oophorus cells together
Fertilization steps
acrosome binds which receptor on the ovum (zona pellucida) to initiate entry into the ovum?
Acrosome binds to ovum via Z3 receptor on the ovum
Acrosome reaction
Entry through zona pellucida
Fusion of cell membrane
Entry of sperm nucleus into ovum cytoplasm
role of the medial preoptic area of the hypothalamus in sex behavior
that region has high conc’s of what?
what happens when this area is stimulated vs if there’s a lesion in the area?
MPOA; Medial preoptic area of the hypothalamus = area of the brain that controls male sexual behavior
Has high concentrations of androgen and estrogen receptors
If lesion, males lose interest in sex
If stimulate, males lose interest in everything but sex
effect of aging on testo levels
what are the symptoms that showed up with decreasing testo levels?
when measuring testo, which do you measure? bound or free? why?
As people age, testo levels decline
Symptoms:
Loss of libido
Loss of vigor
Obesity
Depression
Lack of concentration
Disturbed sleep
Type 2 diabetes
Hot flashes
Erectile dysfunction
Measure bound (to SHBG); free testo is really hard to measure
what is andropause and what does that have to do with testo levels?
features of andropause (what happens to # of sertoli and leydig cells? what happens to testo diurnal rhythm? androgen negative feedback sensitivity? spermatogenesis and libido?)
age-dependent decline of circulating testosterone below the level of a healthy 30-35 year old man (typically 300ng/dl)
decreased Number of Leydig and Sertoli cell number
Gradual decrease in serum testosterone and inhibin
Loss of testosterone diurnal rhythm
increased Androgen negative feedback sensitivity
Osteoporosis, decreased spermatogenesis and libido
what’s the effect of time of day on testo levels and how does this change based on age?
Testo levels highest in the morning, lower during the day (still the same is older men, but it is attenuated
2 categories of sexual development disorders
46 XY and 46 XX
Classifications of 46 XY DSD (the broad categories)
Disorders of testicular development
Disorders of androgen synthesis
Classifications of 46 XX DSD
Disorders of ovarian development
Androgen excess
Disorders of testicular development
Disorders of androgen synthesis
Complete and partial gonadal dysgenesis
Complete and partial androgen insensitivity
Disorders of AMH/ AMH receptor
Androgen biosynthesis defects
Disorders of ovarian development
Androgen excess
Gonadal dysgenesis
CAH
Hypospadius definition
how is epispadius different from hypospadius?
Types of hypospadias
Urethra doesn’t come out the tip of the penis; instead the penile shaft hasn’t fused normally
Epispadius – urethra comes out of the dorsal surface
Glandular
Subcoronal
Distal penile
Midshaft
Proximal penile
Penoscrotal
Scrotal
Perineal
Causes of hypospadius
Genetic
Hormone imbalance
Maternal age and obesity
Fertilization treatments
Placental insufficiency
Maternal vegetarian diet
what’s the effect of congenital adrenal hyperplasia on genitalia development?
what’s the most common cause of this disorder?
Leads to virilization of genitals
21 hydroxylase deficiency = most common
Androgen insensitivity syndrome definition
cause (most common)
phenotype
spectrum of AIS stages
partial or complete impairment of androgen receptor (body makes androgens but the receptor doesn’t work)
usually spontaneous mutation
XY phenotypic female with undescended testis and blind ended vagina
role of estrogen in testicular development
role of estrogen in bone growth
effect of estrogen receptor mutation/lack of estrogen
Must remain inactive for normal testicular development
Critical to final ossification of cartiligenous plates at ends of bones at puberty
If you didn’t have estrogen, you wouldn’t fuse the epiphyseal plates and you’d just keep growing
