Lecture 03, 04, & 05: Male Sexual Differentiation

Chromosomes in a male mammal

XY

Reasons the X chromosome is essential for life

* codes for enzymes found in glycolysis and other biochem paths
* codes for blood clotting factors
* XIST gene: important in females
* AR gene: codes for androgen receptors
* DAX-1 gene: sex determination on X for both M and F

What is the significant gene on the Y chromosome

SRY gene

Why is the SRY gene significant

It codes for SRY protein, which is responsible for activating other genes, specifically ones that cause the bipotential undifferentiated gonads to differentiate into testes

Describe characteristics of PGCs

* large
* have pseudopodia
* motile: amoeboid movement
* secretes lytic enzymes

Where do PGCs originate

The embryonic yolk sac

Where to PGCs migrate to

Gonadal ridge

Chemotactic agent produced by gonadal ridge that signals PGCs to migrate

Telepheron

What causes the formation of primitive sex cords

PGC mitosis produces lots of debris that collects into strands of tissues, and these are the primitive sex cords

What causes the formation of undifferentiated bipotential gonads

Compaction of primitive sex cords

What causes the differentiation of the bipotential gonads

SRY protein activates genes for differentiation into testes

Ultimate fate of PGCs

Spermatagonia

Once compacted and differentiated, what does the SRY protein do to the primitive sex cords

They are differentiated into the seminiferous tubules

What causes the production of Sertoli cells

SRY protein activates the SOX9 protein, which makes Sertoli cells

What causes the production of Leydig cells

SRY protein, and possibly SOX9, activates DHH protein, which produces Leydig cells

List the 3 steps of testicular descent/scrotal formation

1. Nephric displacement
2. Transabdominal phase
3. Inguinal-scrotal phase

List the 3 pertinent developmental urogenital ducts

* mesonephric duct
* paramesonephric duct
* metanephros

What does the mesonephric duct become and how does it get there

The mesonephric duct goes from fetal kidney system to regression, then testosterone differentiates it into epididymis, ductus deferens, and seminal vesicles.

What does the paramesonephric duct become and how does it get there

The paramesonephric duct regresses in males due to AMH from Sertoli cells

What does the metanephros become and how

It becomes the functional kidney and gets larger, no hormonal intervention needed

What does the urogenital sinus become and how

It is differentiated by testosterone into the prostate gland, bulbourethral glands, and urethra

Describe the first phase of scrotal formation

Nephric displacement occurs early in embryonic development, and is the only step in non-scrotal species. This is where the metanephros rises up to become the renal system, and all other ducts regress or move down to become the internal genitalia.

Describe the second phase of scrotal formation

The transabdominal phase occurs early in embryonic development in species with external gonads. The testis is held retroperitoneally (behind the peritoneum) and is both suspended and held down by the gubernaculum ligament. The caudal gubernaculum is attached to the peritoneum at the inguinal ring.

What hormone triggers testicular descent by pulling down on the gubernaculum

Insulin-like 3 from Leydig cells

Describe the third phase of scrotal formation

In the Inguinal-scrotal phase, the gubernaculum swells due to testosterone, forming an evagination of the peritoneum. the evagination grows into the inguinal canal which the testes are drawn through and into the scrotum by a regression of the gubernaculum. After the testes descend, the blood supply and ductus deferens follow. Once everything is in the new scrotum, the inguinal ring constricts to prevent movement of testes out or intestines in.

List the 3 undifferentiated tissues/areas of the male external genitalia

* genital swelling
* genital fold
* genital tubercle

What differentiates the external genitalia tissues

Dihydrotestosterone

What does the genital swelling become

Scrotum

What do the genital folds become

They fuse into the shaft

What does the genital tubercle become

Glans

How is DHT formed

Testosterone reacts with the enzyme 5a-reductase

Describe the glans

It is the specialized distal end of the penis, and is heavily innervated with sensory neurons

Where is the hypothalamus

Below and in front of the thalamus

List the 2 areas of the hypothalamus

* tonic center
* surge center

Function of the tonic center

Control center, regulates hormone levels

Function of the surge center

Causes ovulation in females, regresses in males

What causes the regression of the surge center

Estradiol

How is estradiol formed

Testosterone reacts with the enzyme aromatase

When is initial behavioral change caused in males

In gestation

What are the 2 regions of the hypothalamus critical for sexual behavioral differences

* preoptic nucleus
* ventromedial nucleus

Function of the preoptic nucleus

* thermoregulation
* gonadal hormone regulation
* sexual arousal
* sexual behavior

Compare the preoptic nucleus of males with that of females

The PON is 2-3 x larger in males than in females

Function of the ventromedial nucleus

* mating behaviors and aggression in males
* sexual receptivity in females

Compare the ventromedial nucleus of males with that of females

Males have greater neuronal density in the VMN than females