Male Reproductive Physiology Flashcards

1
Q

Make up of male X and Y chromosome

(what are PAR, SRY and MSY)

A

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

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2
Q

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)

A

Bipotential gonad

+SRY; SOX9 = male

(no SRY) FOXL2, WNT4, FST = female

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3
Q

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

A

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

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4
Q

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

A

the mesothelium, the underlying mesenchyme, and the primordial germ cells

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5
Q

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?

A

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

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6
Q

External genitalia differentiation:

what do the following become in males vs females:

genital tubercle, folds, swelling

A

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

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7
Q

process of testicular descent

A

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

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8
Q

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)

A
  • 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
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9
Q

Basic male genitalia anatomy (just memorize it)

A
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10
Q

Testis anatomy (what are the parts and describe the path that sperm travel)

A
  • 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
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11
Q

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?)

A

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

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12
Q

Leydig cells

…also called what?

where are they? they have receptors for who?

what do they do?

A

Also called interstitial cells

Located between the seminiferous tubules

Have receptors for LH, not FSH

Make testosterone

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13
Q

Sertoli cells

…also called what?

where are they? they have receptors for who?

what do they do?

A

Nurse cells

Make anti-Mullerian hormone

  • Aromotize testosterone to estrogens
  • Form blood-testis barrier; support germ cells
  • Produce androgen binding protein, inhibin, seminal fluid
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14
Q

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?

A

-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

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15
Q

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?

A

-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

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16
Q

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)

A

Increased SHBG

Aging

Cirrhosis

Hyperthyroidism

Anticonvulsants

Estrogens

HIV infection

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17
Q

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)

A

Decreased SHBG

Obesity

Nephrotic syndrome

Hypothyroidism

Glucocorticoids

Androgens

Progestins

Diabetes Mellitus

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18
Q

Androgren receptor domains

how does the receptor get activated/what’s the downstream effect

A

Receptor has N terminal domain; double helix binding domain; and ligand binding domain

See diagram

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19
Q

Functions of androgen in males

A

Differentiation of internal and external male genitalia

Stimulates bone growth

Initiation and maintenance of spermatogenesis

Stimulate and maintain binding proteins and secretory fluids

Behavior

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20
Q

What’s testo secretion going to look like over a lifespan? (see graph below)

A

Spikes of testo in fetal and neo-natal period; there’s a dormant phase for a while until puberty hits

21
Q

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)

A

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

22
Q

Tanner staging for pubic hair growth (aka ___?)

A

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

23
Q

Explain the graph below

why are dudes generally taller than girls?

A

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

24
Q

factors regulating timing of puberty

A

Neural signals

Nutrition

Environmental factors

Genetic factors

25
Q

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

A
  • 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!!)

26
Q

Roles of Leptin and kisspeptin

how is the timing of puberty related to kisspeptin?

how are steroids involved?

A

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)

27
Q

precocious puberty

cause

difference between central and GnRH independent

A

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
28
Q

Delayed puberty definition

causes

diff between primary and secondary hypogonadism

A

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

29
Q

Spermatogenesis requires __ and has to occur at __ temps than body temp

Define the following in terms of spermatogenesis

Spermatocytogenesis

Meiosis

Spermiogenesis

Spermiation

A

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

30
Q

Spermiogenesis

A

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

31
Q

Spermiation

__ stimulates the ___, which activates plasmin, needed for spermiation.

A

Release of spermatozoa from luminal surface of Sertoli cells

FSH

plasminogen activator

32
Q

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)

A

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

33
Q

categories of semen analysis (characteristics of each)

Risk factors for abnormal semen analysis

A

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)

34
Q

Acrosome definition

2 enzymes in the acrosome that carry out the acrosome reaction

A

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

35
Q

Fertilization steps

acrosome binds which receptor on the ovum (zona pellucida) to initiate entry into the ovum?

A

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

36
Q

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?

A

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

37
Q

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?

A

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

38
Q

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?)

A

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

39
Q

what’s the effect of time of day on testo levels and how does this change based on age?

A

Testo levels highest in the morning, lower during the day (still the same is older men, but it is attenuated

40
Q

2 categories of sexual development disorders

A

46 XY and 46 XX

41
Q

Classifications of 46 XY DSD (the broad categories)

A

Disorders of testicular development

Disorders of androgen synthesis

42
Q

Classifications of 46 XX DSD

A

Disorders of ovarian development

Androgen excess

43
Q

Disorders of testicular development

Disorders of androgen synthesis

A

Complete and partial gonadal dysgenesis

Complete and partial androgen insensitivity

Disorders of AMH/ AMH receptor

Androgen biosynthesis defects

44
Q

Disorders of ovarian development

Androgen excess

A

Gonadal dysgenesis

CAH

45
Q

Hypospadius definition

how is epispadius different from hypospadius?

Types of hypospadias

A

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

46
Q

Causes of hypospadius

A

Genetic

Hormone imbalance

Maternal age and obesity

Fertilization treatments

Placental insufficiency

Maternal vegetarian diet

47
Q

what’s the effect of congenital adrenal hyperplasia on genitalia development?

what’s the most common cause of this disorder?

A

Leads to virilization of genitals

21 hydroxylase deficiency = most common

48
Q

Androgen insensitivity syndrome definition

cause (most common)

phenotype

spectrum of AIS stages

A

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

49
Q

role of estrogen in testicular development

role of estrogen in bone growth

effect of estrogen receptor mutation/lack of estrogen

A

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