HPG Axis, Estrous Cycle, Fertilization, Sexual Differentiation

Block 6

What is the male reproductive system regulated by?

Hypothalamic Hypophyseal Gonadal (HPG) Axis

Male reproductvie anatomy:

testes

seminiferous tubules

epididymes

Male duct system (ductus deferens, seminal vesicle, ejaculatory duct

external genitalia

accessory sex glands

What two cells do Testes contain?

Leydig (intersititial space)

Sertoli (seminferous tubules)

What is the seminferous tubule?

site in testes where sperm cells develop and mature

Epididymides purpose:

transport and sotrage of sperm

tail of epididymis is sesnsitive to oxytocin

What does male duct system turn into?

Wolffian ducts (made of ductus deferens, seminial vesicle, ejaculatory duct

External male genitalia

penis

scrotum

Where is GnRH secreted

Secreted: tonic center of hypothalamus

Travels: primary portal plexus to anterior pituitary

Triggers: release of LH and FSH

What is Lutenizing hormone target?

Leydig (intersitital cells)

Stimulates them to convert cholesterol into testosterone

What does FSH target?

Sertoli cells

support spermatogenesis (sperm production)

secretion of two regulatory proteins (ABP and Inhibin)

What is ABP secreted from?

Sertoli cells into the lumen of seminiferous tubules

w

What does ABP do?

acts as sponge to concentrate testosterone locally

ensures testosterone in tubules are hundreds of times higher than the blood

Purpose of testosterone:

supports sperm production

negative feedback to hypothalamus and pituitary to slow down production of GnRH and LH

What produces Inhibin?

Sertoli cells

negative feedback to inhibit FSH

what does simple neural reflex do?

Stimuli (tactile, thermal) trigger impulses to spinal cord resulting in skeletal muscle for ejaculation and sexual behavior

Scrotal regulation

smooth muscle responds to stimuli to maintian scrotal tone and trigger scrotal sweating

What regulates female reproductive system?

hypothalamic hypohyseal gonadal axis: using two center hypothalamic system

Female anatomy:

ovaries, oviducts, uterus, cervic, vagina, external genitalia (clitoris, labia)

hypothalamus

Purpose of ovaries:

primary gonad responsible for producing oocyte and steroid hormones

house folliicles (containing granulosa, and theca cells) and the corpus luteum (CL) which forms after a follicle ovulate

Purpose of oviducts:

derived from paramesomephric ducts

transports gametes

ampulla of oviduct is where fertilization occurs

where does fertilization occur?

ampulla of the oviduct

purpose of uterus

site of embryo development and produces prostoglandin to regulate cycle

purpose of cervix

barrier to utuers

hypothalmus centers in female

tonic center (basal hormone release)

Surge center (triggering ovulation)

Where is GnRH secreted in females?

secreted by hypothalmus to stimulate the anterior pitutitary to release FSH and LH

what does FSH do in females?

target granulosa cells in ovary

promotes follicular growth and stmiulate the converstion of andgrogens into estradiol

what does LH do in females?

stimulates theca internal cells to produce androgens

What causes ovulation?

massive bucket-like dump of GnRH from surge center triggers preovulatory LH surge

Estradiol purpose:

produced by growing follicle

facilitiates signs of heat (standing estrus)

at high concentrations without progesterone provides positive feedback to the surge center to trigger ovulation

When and where is progesterone produced?

produced by corpus luteum during luteal phase

Purpose of progesterone

brake on system

provides negative feedback to inhibit GnRH and LH

maintains pregnancy and prevents further ovulation

Where is inhibi produced in females?

granulosa cell

Purpose of Inhibin?

Suppress FSH secretion

helps select dominant follicle

Where is prostoglandin produce in female?

secreted by utuerus if no pregnancy is detected

Purpose of prostoglandin?

cause luteolysis (desctruction of CL) to end the luteal phase and restart the cycle

Purpose of reproductive system:

gamete production and maturation, sexual receptivity, fertilization and transport, pregnancy maintenance, milk let-down

Gamete production and maturation occurs when?

ovaries produce mature oocytes capable of being fertilized following the LH surge

Sexual receptivity occurs how:

high estradiol levels during follicular phase induce behaviors like lordosis (mating posture) and increased physical activity to ensure mating occurs

fertilizaiton and transport occurs by:

producing mucuos and increased smooth muscle motility under estrogen influence to assist sperm transport toward ovidcut

pregnancy maintence occurs:

if fertilization is successfule, progesterone dominates to quiet uterine activty and support developing embyro

Milk let-down occurs:

the hormone oxytocin which is released by posterior pituitary targets the mammary gland to facilitate lactation.

GnRH:

produced by:

Target organ:

Function”:

Produced: hypothalms

Target: anterior pitutitary

Function: stimulates release of gonadtropins, FSH, LH

Luteinizing hormone:

Produced: anterior pitutitary

Target: leydig cells and Theca

Function: teststerone production, androgen production and then preovulatory surge triggers ovulation

FSH

produced by: anterior pitutitary

target: Sertoli and Granulosa

Function: supports spermatogenesis and production of ABP

Females: follicular growth and converstion of andgrogens to estradiol

Oxytocin

Produced by: hypothalums (via posterior pitutitary)

Target: taile of epididymis and mammary gland

Function: assists in sperm movment in males and milk let-down in females

testosterone

produced by: leydig in testes

Target: sertoli cells, brain, male reproductive duct system

function: support spermatogeneiss, promotes wolffian ducts, negative feedback to brain

Estrodiol

produced: granuolsa cells of the ovarian follicle

Target: brain and female reproductive tract

Function: responsible for sexual receptivity, stimulates reproductive tract secretions, regulates GnRH/LH through positive and negative feedback

Progesterone

produced by: corpus lutuem on ovary

target: hypothalamus, pitutitary, uterus

FunctioN: pregnancy hormone, maintains pregnancy, inhibits estrous behavior, acts as brake on GnRH and LH

Inhibin

produced by: sertoli cells and granulosa cells

target: anterior pituitary

function: inhibits secretion of FSH

Prostoglandin

Produced: uterine endometrium

Target: corpus luteum

Function; causes luteolysis (regression of CL), ending progesterone production to allow a new cycle to begin

Melatonin

produced by: pineal gland during darkness.

Target: hypothalamus

Function: regulates seasonal cyclicity in species like horses and sheep by promoting or inhbiting GnRH release

Anti-mullerian hormone (AMH)

produced: sertoli cells in fetal testes

Target: paramesmephric duct

function: causes regression of the femle ducts during male fetal development

Dihyrotestosterone (DHT)

produced by: converted from testosterone in peripheral tissue

Target: undifferentiated exteranl genitalia

Function: drives the differentiation of male external genitalia such as penis/scrotum

Androgen Binding protein (ABP)

produced by: sertoli cells

target: lumen of seminiferous tubules

Function: spong to concentrate testotserone locally

polyestrus

animals cycel regularly throughout the year (cattle, pigs, rodents)

Seasonally polyestrus

species cycle regularly only during specific seasons dictated by day length and melatonin levels

long day breeders

cycle duing spring/summer when days are longer

horses

short day breeders

cycle during autumn/winter when days are shorter

sheep, goats, deer

monoestrus

animals have only one or two cycles per year

dogs, wolves, bears

follicular phase

20% cycle

dominance of follicles on ovary and primary

hormone: estrodiol

ends; ovulation

Luteal Phase

80%

Function: presence of corpus luteum (CL)

Hormone: progesterone

Lasts: ovulation until regression of CL

Proestrus (follicular phase)

transition where progesterone dominance ends and estrogen dominance begins

Estrus (Follicular Phase)

sexual receptivity

standing heat

metestrus (Luteal Phase)

transition from estrogen dominance to progesterone dominance following ovulation

What is special about cattle metestrus?

metestrust bleeding from the vulva

Diestrus (Luteal phase)

longest stage

maximum luteal function

high progesterone levels to maintain a potential pregnancy

Induced ovulators

cats, rabbits, ferrets, llamas

do not ovulate automatically, mating is required to trigger LH surge

The Queen:

seasonally polyestrus and induced ovulators

if not mated they remain in constant state of receptivity, exhibity estrus signs every 2-10 daysA

Anestrus

female stops cycling from:

pregnancy, lactation, seasonality, stress, disease.

Fertilization requires both gametes to be transported to

ampulla of the oviduct

Capacitation

sperm removes seminal proteins and reorganizaes the plasma membrane

capacitated sperm are hyperactivtated motility

what does capacitated sperm bind to?

zona pellucida (thick outer layer of oocyte)

After capacitated sperm binds to ZP what happens?

acrosome reaction: sperm releases digestive enzymes from its head to penetrated ZP

ZP penetration

uses enzymes and hyperactivited motility to penetrate and enter perivitelline space

what happens after zona pellucida penetration?

secondary binding (fusion) adheres to ooplasma and activates the oocyte

oocyte activation triggers:

cortical granule exocytosis where causes ZP to hardent and block other sperm

What happens after activation and hardening of ZP?

meiosis resumption

rleases a second polar body

Pronuclei formation

sperm head forms Male pornucleus (1N) and female pronucleus (1N)

syngamy and embryo development

two haploid pronuclei fuse together to restore the diploid (2N) state and mitotic division begins

this marks the start of embyro development

sperm requirment for successful fertilization

capacitation

hyperactivtiated motility

acrosome reaction

oocyte requirement for succesful fertilization

complete nuclear maturation (meiosis resumption)

cytoplasmic maturation (migration of cortical granules)

successful development requrements of successful fertilization

effective boock to polyspermy and full oocyte activation

Alpha-fetoprotein in females:

Binding: alpha-fetoprotein has high affinity for estradiol

Barrier: because when it estradiol and alpha-fetoprotein are bound it is too large to cross blood/brain barrier

Result: brain is not exposed to estrogen which allows for surge center to develop

Alpha-fetoprotein in males:

No binding: testosterone does not bind to alpha-fetoprotein

Crossing barrer: unbound testosterone can cross blood-brain berrier into hypothalamus

Conversion: aromatase converts testosterone into estradiol

Result: presence of local estraiol in brain “defminizes” the hypothalamus and prevents development of surge center

Freemartinism

cattle, if female is born co-twin to male, placental connections allow male AMH and testosterone to enter females circulation

result: masculinzation of the female twin leading to incomplete reproductive tract and infertility

calico cats:

phenotype is a result of x-inactivation

orange/black are X chromosome

males are rarely calico unless extra X

Klinefelters syndrome xxy

extra x crhomosome

What happens in freemartinism to ducts

segmental aplasia (female mullerian duct) fails to develop completley or fuse properly

leads to incomplete reproduction tract

may develop male-like structures

Exogenous masculinization

if a pregnant animal is supplemented with excess progesterone during mid-gestation the progesterone can be converted into androgens

Result: masculiniation of female fetus

Granulosa theca Cell Tumor

this tumor affects specialized cells of ovary (theca/granulosa)

tumor causes theca cells to produce excessive testosterone

What are protein hormones?

LH, FSH< GnRH, Oxytocin

large, must bind to membrane receptors on cell surface to activtate signaling cascade

What are steroid hormones?

testosterone, estrogen, progesterone

fat-soluble

can enter and bind to nuclear receptors inside nucleus to activate gene transcription

What converts ATP to cAMP?

adenylate cyclase

What does cAMP activate?

protein kinases which lead to synthesis of new protein products for reproduction

Process of LH

LH binds to membrane receptor

2. receptor activates G Protein which activates adenylate cyclase

3. adenylate cyclates converts ATP into cAMP

   1. cCMP actiates protein kinases which leads to synthesis of new protein products for reproduction

cholesterol has how many carbons?

27

21 carbon steroid

progesterone

19 carbone steroid

testosterone

18 carbone steroid

estrogen

How are steroids inactivated?

liver inactivates via conjugation

once inactivated can reenter blood through kidney and excrete in urine

bile route are excreted in feces