Sex Differentiation

Differentiation =

Primitive group of unspecialized cells develop a functional and specialized group of cells that provide a common function

Involves Formation of Three Germ Layers:

• Embryonic tissue which form all adult tissues and organs

• Ecto, meso, endoderm

Germ Layers formed during:

Gastrulation (re-arrangement of the embryonic cells)

Genetic Differentiation:

• Genetically determined by the presence of Y chromosome

• Takes place at fertilization

  • Sperm delivers an X (female)

  • or Y (male) chromosome

Sry gene of Y chromosome causes:

undifferentiated gonad to develop into testis

• Responsible for expression of testis determining factor (TDF) secreted by sex cords

TDF controls pathway towards:

either male or female development

Sex cords:

structures inside undifferentiated gonad —> like germ cells for gonads

Chromosomal sex —>

gonadal sex —> hormonal sex —> phenotypic sex —> brain and/or behavioral sex

Single Pair of sex chromosomes:

mammals, some but not all vertebrates

Sex is environmentally determined:

sea worms, fish, reptiles

Multiple sex chromosomes:

invertebrates, insects, reptiles

Haplodiploidy:

bees, spiders

What is amniocentesis?

a prenatal medical procedure where a healthcare provider uses a thin, hollow needle to collect a small sample of amniotic fluid from the sac surrounding a fetus

Haplo-Diploid Sex Determination in Bees:

this image

Both male and female gonad and duct system are:

retroperitoneal

• as the gonads and reproductive ducts develop in the embryo, they form behind the peritoneal membrane rather than inside the peritoneal cavity

retroperitoneal =

“outside” the peritoneum

peritoneum =

cavity inside gut — serous membrane that lines the abdominal cavity and covers and supports abdominal and pelvic organs

Before gonadal differentiation:

germ cells form connective tissue in the gonads — not testes or ovaries yet

Development of primordial germ cells in the yolk sac happens during the:

first 15% of gestation

Migration of primordial germ cells from the yolk sac into:

genital ridge

Primordial germ cells =

stimulate connective tissue proliferation & Forming primitive sex cords

Genital ridge:

enlarges and gives rise to indifferentiated gonad

Genital ridge with stimulation of sex cords give rise to:

renal system

What is also developing at the same time as gonadal differentiation?

kidneys

Urine is produced and drained by:

mesonephric ducts (previously called Wolffian ducts)

What functions like the kidneys before they develop?

mesonephric ducts

What ducts becomes the male?

wolffian ducts

Paramesonephric ducts or Müllerian ducts form on:

either side of mesonephric ducts

Which ducts become the female?

paramesonephric ducts

While the mesonephric ducts function as the kidneys, the embryo is still in what stage?

sexually indifferent stage

Development of the urinary system:

• pronephros

• mesonephros

• metanephros

pronephros =

primitive kidney

mesonephros =

closely associated with the unindifferentiated gonad

metanephros =

becomes the functional kidney

Development reproductive tract:

Two distinct tubules structures which give rise to male or female reproductive tracts

a. mesonephric duct (Wolffian Duct; male)

b. paramesonepheric duct (Mullerian Duct; female)

Overall steps of gonadal differentiation?

1. Development of primordial germ cells in the yolk sac

2. Migration of primordial germ cells from the yolk sac into the genital ridge

3. Genital ridge with stimulation of sex cords give rise to renal system

4. Development of the urinary system

5. Development reproductive tract

Eventually, which tract will be connected to the mesonephros?

male

Eventually, which tract will not be connected to the mesonephros?

female

In males, what causes the regression of paramesonephric ducts?

TDF in sex cords

in sex differentiation, does the mesonephric ducts regress in females?

yes

TDF & Sex cords —>

gonad —> testes —> makes sertoli cells

In the presence of Y chromosome and Sry gene…TDF:

• Development of indifferentiated gonad to testes and Sertoli cells

• Secretion of anti-mullerian hormone (AMH) by sertoli cells

• Degeneration of Mullerian duct and development of Wolffian duct

• Differentiation of interstitial Leydig cells

• Secretion of testosterone and development of male reproductive duct system

What hormone causes the regression of mullerian ducts?

anti-mullerian hormone (AMH)

Before testicular descent, what happens?

testes stay put while the body lengthens

Four phases of Testicular Descent: Growth and elongation of

the body away from the stationary testes.

Four phases of Testicular Descent: Rapid growth of

the distal gubernaculum — Results in testes being pulled to the inguinal ring

Four phases of Testicular Descent: Shrinkage of

gubernaculum within scrotum pulls testes through inguinal ring

Four phases of Testicular Descent: Continued regression

of the gubernaculum situates testes within scrotum

Growth and regression of gubernaculums: Testicular factor

“descendin” has been shown to cause growth in gubernacular cells in vitro

Growth and regression of gubernaculums: Testosterone

or gonadotropins do not appear to play a major role in gubernacular growth

Growth and regression of gubernaculums: Intra- abdominal

pressure may play a larger role in the movement of testes from abdomen and into scrotum

Testes Fail to Descend?

Cryptorchid

Cryptorchid =

a. bilateral: both testes retained: sterile

b. unilateral: one testis retained: fertile-sub-fertile

Hormone production in cryptorchid males?

Hormone production is NOT decreased — will exhibit secondary sex characteristics and normal reproductive behavior

Cryptorchidism is:

heritable & likely that fertility will be compromised, so therefore cull

Possible to surgically or with pharmaceuticals:

lower retained testis

Descent of testes into the scrotum occurs: Bull & Ram

mid-gestation

Descent of testes into the scrotum occurs: Boar

last quarter of gestation

Descent of testes into the scrotum occurs: Stallion

just before birth/ at birth

Why are bilateral cryptorchids sterile?

• Temperature regulation!

• The temperature requirements for normal spermatogenesis must be different

If increase temperature of scrotum/insulate against heat loss:

• If increase temperature of scrotum/insulate against heat loss

• Increased # of abnormal sperm=decreased fertility

Female vs male formation?

female is inverse to everything talked about in the male

Female in the absence of Sry Gene:

• No TDF

• Development of ovaries

• No Sertoli cells

• Absence of AMH

• Degeneration of Wolffian duct and development of Mullerian duct

• Development of female reproductive tract

In the absence of testis determining factor:

• cells in the sex cords differentiate into follicular cells

• Genital ridge becomes ovary

in the female, ____ hormone is present?

müllerian

What cells produce the müllerian hormone?

follicular cells

Rete tubule formation in females:

is less pronounced and never connects, therefore there is no “tube” leading from ovary to oviduct

Rate tubules are part of:

mesonephric duct

ovary & oviduct are not:

physically connected

In females, Paramesonephric ducts become:

• the oviduct, uterus, cervix, and vagina

• The degree to which these ducts fuse determines the type of uterus

• 
  

Females — Tubules fuse with urogenital sinus:

this creates the opening to the outside

Caudal vagina and vulva form from:

the ectoderm

Freemartinism =

• Abnormal embryogenesis of the female reproductive tract

• When twins are present, chorion (extraembryonic membranes) fuse so there is a common blood supply between two calves

• So both conceptuses are exposed to same hormones, including testosterone and anti-müllerian hormone

Developmental effects of femartinism?

• super short tract & not very developed horns

• blind tract

How is the brain defeminized?

testosterone crosses the blood brain barrier and turns into estrogen — the estrogen inside the barrier defeminizes is and makes her not develop a surge center

No surge center =

no ovularion

The Freemartin in Cattle:

• Female born twin to a bull

• Placenta membranes of the 2 fetuses fuse

• Common blood supply

  • At time of testis formation (d 40) 

  • Before ovarian formation

At day 40, the main thing is:

AMH functioning

In fremartin females, testosterone:

coms from male first & later they build their own supply but they don’t have sertoli cells

Both fetuses:

• share a common hormone environment

• Testosterone & anti-mullerian hormone

• Animals are chimeric (share blood types/WBC from other twin)

• TDF (SRY) expressed in both individuals

AMH from bull - blocks Mullerian ducts & causes in some cases:

Posterior vagina, no anterior vagina

Testosterone from bull causes:

• clitoral enlargement

• Brain changes like that of male

Ovaries do not grow but are chimeric:

Ovotestis — partial development of each system

• SRY and therefore AMH and Testosterone

• Further changes and adult male behavior

• acts more like a male

Freemartins can be used as:

Use as estrus detector — “gomer bulls”

“gomer bulls” =

an intact, sexually mature bull that has been surgically altered so he can find and mount cows in heat, but cannot impregnate them

When do testes typically develop?

~ day 35

When does the female tract develop?

~ day 40

What image needs to be known well?

this flow chart

HD =

Hypothalamic Differentiation

HYPOTHALAMIC GNRH SURGE CENTER IS NECESSARY FOR:

INITIATION OF THE ESTROUS CYCLE AND FOLLICULAR OVULATION IN THE FEMALE

HD in Male — Defeminization (Masculinization) of the brain in the male:

1. T from the fetal testis reaches the brain

2. T is converted to estradiol by aromatase enzyme in the hypothalamus

3. Regression of the hypothalamic GnRH surge center by estradiol

4. Defeminization of the hypothalamus (no surge center)

HD in Female — If synthesis of estradiol in the hypothalamus responsible for defeminization of the surge center, why doesn’t the female (with a lot circulating estradiol) become “defeminized”?

Estradiol in female binds with liver protein called alpha-fetoprotein

• New complex cannot cross blood brain barrier where the surge center is located

• Estradiol cannot affect the GnRH surge center