Male Reproductive Physiology

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what is produced at the end of meiosis II

early spermatids are the result of meiosis II

what is the effect of estradiol on HPG axis

estradiol has a profound negative feedback effect on the hypothalamus and pituitary

where is estradiol produced in men

estradiol is produced in the testicle and in the adrenal gland

what is the role of exogenous testosterone

exogenous testosterone prevents the body from making its own testosterone -- means that you dont get sufficient spermatogenesis

what does exogenous testosterone do

exogenous testosterone suppresses both endogenous testosterone (decreased LH) and sperm production

what are DHT functions

external masculinization and sexual maturation at puberty

what are the symptoms of hypogonadism

fatigue, irritability, depression, lacking endurance, unable to build muscle, trouble sleeping, and low libido

what is the adluminal compartment of the blood-testis barrier

germ cells undergoing differentiation and maturation

how do you treat kallmann syndrome

give supplemental FSH and LH when trying to conceive. give supplemental testosterone eventually after done conceiving

what are testosterone functions

gonadotropin regulation, spermatogenesis, sexual differentiation (wolffian stimulation)

why do spermatazoa need protection from immune system

haploid cells have unique antigens that are not recognized as self. also there are anti-sperm antibodies that can give you autoimmune orchitis

isolated spermatogenic failure

have normal testosterone and function, but have another issue with sperm production - ex. from prior chemo/radiation

biopsy protocol for non-obstructive azoospermia

have to do more than one biopsy because there could be focal areas with complete spermatogenesis amidst a majority of abnormal tubules -- want to look for the functioning pockets if they're there

what pulse favors LH?

high pulse frequency of GnRH favors LH secretion

what happens with LH and FSH in infancy and early childhood

hypothalamus is very sensitive to steroid negative feedback -- very low GnRH and FSH/LH secretion prior to puberty

what is the basal compartment of the blood-testis barrier

immature germ cells and stem cells make up the basal component

what is the role of estrogen in the male system?

in males, estrogen has a profoundly negative effect on the HPG axis

how is seminiferous tubule structure related to spermatogenesis?

in most people, sperm production in the testicle is homogenous and the sperm migrate to the lumen as they are developing

What is the bound:unbound ratio of testosterone in the plasma

in the plasma, ~60% of testosterone is tightly bound to SHBG

what is the effect of inhibin on the HPG axis

inhibin has a negative feedback effect on the pituitary and directly affects FSH secretion

which cells produce inhibin

inhibin is produced by sertoli cells which reduces pituitary FSG output

what is in the testis interstitium

interstitium between tubules contains blood vessles, lymphatics, and leydig cells

what is the importance of the blood-testis barrier

it crease an immunologically privileged site for mature spermatazoa

how long does it take for sperm to travel to the epididymis

it takes 12 days and is governed by slow contractions of the muscular wall

is azoospermia common?

its in <2% of men overall, but 15% of men presenting with infertility

what are the genetics of kallmann syndrome

kallmann syndrome is x-linked

what do leydig cells produce and secrete

leydig cells are steroid producing and secrete testosterone

what do leydig cells arise from embryonically

leydig cells arise from mesenchymal cells next to the renal system

how do leydig cells make testosterone

leydig cells have membraine receptors that bind LH, resulting in an increase in intracellular cAMP and protein synthesis

how do leydig cells get to the testis interstitium

leydig cells migrate to the interstitium around early spermatic cords during fetal development

what is in the peritubular compartment of the testis

leydig cells, basement membrane, extracellular matrix, and myofibroblasts

what pulse favors FSH?

low frequency GnRH pulses favor FSH secretion

what is the proliferative phase of spermatogenesis

mitosis is the proliferative phase

what happens with LH and FSH during puberty

nocturnal FSH and LH pulses begin during puberty and the HPG axis resets its sensitivity threshold to steroid feedback

what are the two categories of azoospermia

obstructive and non obstructive -- with non-obstructive being a little more common

where are the testes located

outside the abdominal cavity

what happens with LH and FSH in early fetal development

placental hCG controls the development of the testes and wolffian ducts and pituitary LH takes over as fetal HPG axis matures

pulsatile GnRH rhythm

pulses every 60-180 minutes sending out LH or FSH and is controlled by sex steroid feedback

what is produced at the end of meiosis I

secondary spermatocytes are created in meiosis I

how is GnRH secreted

secreted into the hypophyseal portal system where it has a short half life -- serum levels are too low to detect

where does LH act and what does it do?

LH acts on LH receptors on leydig cells to stimulate synthesis of testosterone

what regulates LH in men

LH is controlled by negative feedback from testosterone and estradiol

how is LH affected by inhbin and activin

LH is not affected by inhibin

why are the testes located outside the abdominal cavity

because the temperature is 35 celsius -- need lower temp for sperm production

how is the blood-testis barrier created

blood-testis barrier is a physiologic barrier created by active transport processes

when are sertoli cells mitotically active

sertoli cells are mitotically active during puberty, but mitotically inactive in adulthood (because of surges of FSH in puberty)

what is the structure of sertoli cells

sertoli cells are polarized cells that extend from the basemement membrane to the lumen

how much of the testis do sertoli cells make up?

sertoli cells comprise 1/3 of the bulk of the germinal epithelium

what kinds of receptors to sertoli cells have

sertoli cells contain membrane receptors that bind FSH, leading to increased intracellular cAMP and protein synthesis

what do sertoli cells do for developing germ cells

sertoli cells engulf and nurture developing germ cells

how do sertoli cells regulate the tubule microenvironment?

sertoli cells govern fluid secretions, phagocytosis, steroid metabolism, sperm production, and sperm movement/development

what cells make up the blood-testis barrier

sertoli cells make up the blood testis barrier

what do sertoli cells secrete

sertoli cells secrete AMH (fetus), androgen binding protein, and inhibin (adults)

what is the half life of LH

short half life - metabolized by the liver with wide variation throughout the day

how do sperm mature in the epididymis

sperm become progressively more motile they traverse the epididymis (this is important for harvesting sperm with IVF/ICSI) and they also gain capacity (necessary for fertilization)

what is the timeline of sperm production

sperm production is a constant process with constantly renewing cycles in different areas -- kind of patchwork pattern rather than wave like. takes ~60 days

what is spermiogeneisis

spermiogenesis is the maturation of spermatids to spermatozoa

what is the pathway of development for sperm through meiosis II

stem cells --> primary spermatocytes --> secondary spermatocytes --> spermatids

what does testis atrophy suggest

testis atrophy suggests low sperm count

what is the main regulator of spermatogenesis

testoserone is the main regulator of spermatogeneis

what is the ratio of testosterone in the testicle vs. in the blood

testosterone concentration in the testis is 100x peripheral concentration

what is the endocrine function of testosterone?

testosterone diffuses into the plasma where 2% is free, and the remained is bound weakly to albumin or tightly to SHBG

what is the paracrine function of testosterone

testosterone diffuses into the seminiferious tubule lumen bound to androgen binding protein (ABP)

what is the effect of testosterone on the HPG axis?

testosterone has a negative feedback effect on the hypothalamus and pituitary - this affects LH and FSH

what protein is testosterone bound to in the blood

testosterone is bound to androgen binding protein (ABP) when traveling in the body

where is testosterone produced

testosterone is produced in the leydig cells and then enters sertoli cells

interplay of LH and FSH with testosertone

testosterone is released in response to LH, but the effect is facilitated by FSH

what is testosterone made from

testosterone is synthesized from cholesterol

how is testosterone converted to estradiol

testosterone undergoes aromatization in adipose tissue to estradiol

how is the blood-testis barrier maintained?

the blood-testis barrier is maintained by dissolution and reassembly of tight junctions

what is the tunica albuginia

the capsule surrounding the functional units of the testis - connective tissue

what is the name of the connective tissue in the testis

the connective tissue capsule is called the tunica albuginea

what else is in the scrotum other than the testes?

the cremaster muscle is also in the scrotum -- descends with the testicle during development

what are the efferent ducts

the efferent ducts drain into the epididymus

what is the endocrine function of the testis

the endocrine function of the testis is to make steroids in leydig cells

what is the exocrine function of the testis

the exocrine function of the testis is to make sperm -- made in the sertoli cells and dependent on the exocrine function

what are the fibrous septa

the fibrous septa are the connective tissue that separate the lobules of the testes

which testosterone is functionally available

the functionally available testosterone is only what is free and what is bound to albumin

where are the leydig cells located

the leydig cells are located in the testicular interstitium

what is the meiotic phase of spermatogenesis

the meiotic phase is the production of haploid gametes (spermatids)

what is klinefelter syndrome

the most frequent sex-chromosome disorder seen in 1/600 boys, 3% infertile men, and 11% of men with azoospermia

what determines the testosterone set point?

the normal set point of testosterone is determined by low levels of circulating T, not intratesticular T

what are the structural compartments of the testis

the peritubular and intratubular compartments and the blood-testis barrier

how long is the process of maturation and transport in the epididymis

the process takes about 78 days

what promotes the production of androgen binding protein

the production of ABP is mediated by FSH

what is the pulsatile secretion of LH

the pulsatile secretion of LH mirrors GnRH -- released about every 2 hours

what is the structure of the seminiferous tubules

the seminiferous tubules are arranged into lobules with 2-4 loops per lobule. they are about 300 m in total length

what comprises the bulk of the testis

the seminiferous tubules comprise the bulk of the testis and are responsible for sperm production

what is in the intratubular compartment of the testis

the sertoli cells and germ cells

what is the primary target for LH and FSH in men

the testis

what happens with GnRH neurons with kallmann syndrome

there is a failure of GnRH neuron precursors to migrate from the nose to the hypothalamus (often also have a diminisehd sense of smell)

what happens during puberty for those with kallmann syndrome

there is a failure to start puberty

what is obstructive azoospermia

this is someone who has blocked the path somewhere between production and ejaculation (ex. vasectomy)

what is non-obstructive azoospermia

this is when you have an issue with the actual production of sperm -- where some bigger process is involved

what do you get after the first meiotic division

two secondary spermatocytes after meiosis II (these cells are genetically different)

what are rete testis

when the seminiferious tubules anastomose

what do you get after meiosis II

you get 4 haploid spermatids

what regulates FSH

FSH regulated by negative feedback by inhibin b, testosterone, and estradiol

what stimualtes sertoli cell function

FSH timulates sertoli cell function

where is GnRH produced

GnRH is produced in the pre-optic anterior hypothalamus

how is GnRH released in men

GnRH is released in a circadian rhythm and in a pulsatile rhythm

how do GnRH neurons get to the hypothalamus

GnRH neurons migrate from the nose to the hypothalamus during development

what is azoospermia

absence of sperm in the ejaculatory fluid

what has a stimulatory effect on FSH

activin has a stimulatory effect on FSH from the pituitary

where does FHS act and what does it do

acts on the FSH receptor in sertoli cells and stimulates spermatogenesis

GnRH and circadian rhythms

24 hour cycle that is controlled by melatonin output from the pineal gland. you have greater GnRH action in the early morning -- this is therefore when you have the highest levels of LH and testosterone

what percent of couples become pregnant after one month of trying

25% pregnant after 1 month

what is the most common genotype in klinefelters

47, XXY in 80-90% of klinefelter's -- small percent are mosaic

how is testosterone converted to DHT

5-alpha-reductase is the enzyme that converts testosterone to DHT

where are the sperm stored in the epididymis

60% of the sperm are stored within the tail (Cauda) of the epididymis

how many sperm are stored in the epididymis

700 million sperm are stored

what precent of couples will become preganant after 1 year

85% pregnant after 1 year

what percent of couples have difficulty conceiving

15% have trouble getting pregnant

how do you diagnose klinefelter's

1. amniocentesis 2. learning difficulties and behavioral problems in childhood - possibility for cognitive deficits 3. lack of masculinization and small testes (atrophic) during puberty 4. infertility in adulthood

what happens to primary spermatocytes in meiosis I

1. chromosome reduplication 2. synapsis 3. crossing over 4. homologous recombination

what are the 4 ways sertoli cells support spermatogenesis

1. create specialized microenvironment 2. expose germ cells to high levels of testosterone 3. coordinate maturation via gap junctions between SC and GC 4. transport differentiating GC towards the lumen

how do sperm get from the testis to the epididymis?

1. fluid pressure in the seminiferous tubule 2. myoepithelial contractions of the tubules or the tunica albuginea 3. cilia within efferent tubules

what happens during spermiogenesis?

1. nuclear condensation and repackaging of DNA from histones to protamines 2. acrosome formation 3. residual body separation from the sperm 4. tail formation (Develops from centriole)

what does androgen binding protein do

ABP binds testosterone in the tubules and keeps the testosterone in the testicles

What receptors does DHT bind to

DHT binds to the same receptors as testosterone but with higher affinity

what is the half life of FSH

FHS has a longer serum half life -- these levels remain relatively steady

what iskallmann syndrome

a syndrome of hypothalamic disfunction - congential hypogonadotropic hypogonadism


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