Cluster

SRY

found how: Looking for Tdf region (testis-determining factor)

controls a cascade of genes that make the testes develop

ovary develops in the absence of SRY

External genitalia

Undifferentiated phallus becomes a penis OR clitoris

Undifferentiated fold becomes the scrotum or vaginal labia

Each of the two typical sexes develops one or the other, the each come from the same undifferentiated precursor!

Internal genitalia 

Müllerian ducts become the oviduct, uterus, and upper vagina


Wolffian ducts become deferent seminal duct and associated glands


Both sexes as embryos initially possess both Müllerian and Wolffian ducts

FRANK LILLIE - hormonal determinants of sexual phenotype

The “freemartin effect”:

Twin calves, one typical male and one intersex

intersex calf was genetic female masculinized by hormones

Wolffian and Müllerian ducts (internal genitalia): the presence of the male reduces Müllerian ducts and enhances Wolffian ducts in the genetic female

**Male hormones can masculinize the body of female

ALFRED JOST

Removed gonads from fetal rabbits, then put the fetuses back in the womb (incredibly difficult process!!). “Take it away” experiment

Castration of males caused: Müllerian ducts persisted. Wolffian ducts regressed. External genitalia = feminine!

**descoverd a hormone secreted by the testes that causes Müllerian ducts to regress (MIH/AMH)

Without __ you don’t have enough testosterone and __ to masculinize development.

Sry, AMH

organizational effect of hormones

permanent, structural changes to the brain and body caused by sex steroids (e.g., testosterone, estrogen) during critical developmental periods, primarily prenatally or perinatally

X-inactivation

Because females have two X chromosomes, one X in each cell is mostly “turned off.”

This prevents females from producing double the amount of X-linked gene products.

It happens early in development and is random in each cell.

Xist (X-inactive specific transcript)

is a gene that produces RNA.

This RNA coats one X chromosome and triggers its inactivation.

It helps silence most genes on that X chromosome.

X escapees

Not all genes on the inactive X are fully silenced.

X escapee genes are genes that still get expressed from the “inactive”

X. This means females can express some X-linked genes at higher levels than males.

Dosage Imbalance

Refers to differences in gene expression levels between XX and XY individuals.

Even though X-inactivation helps balance this, it is not perfect.

Escape genes and Y-chromosome differences still create unequal gene dosage between sexes.

Mosaic expression

Females are mosaics for X-linked gene expression.

Because each cell randomly inactivates one X, different cells express different X alleles.

This creates a patchwork pattern of expression across tissues.

2/2+ genotypes/gene expression with an signal org

Organizational vs Activational effects

Organizational effects

• Permanent changes during early development (especially prenatal/early postnatal)

• Shape brain and body structures long-term

• Example: testosterone during development masculinizing certain brain circuits

Activational effects

• Temporary effects that depend on current hormone levels

• Influence behavior and physiology in adulthood

• Example: testosterone increasing aggression or libido in adult