Sex Determinants & Disorders

What are the three levels of sex differences?

Genetic (chromosomes), gonadal, and phenotypic.

Which sex chromosome combination corresponds to males?

XY.

Which sex chromosome combination corresponds to females?

XX.

What determines genetic sex?

The sex chromosomes inherited at fertilization.

What are the male gonads and female gonads?

Male: testes; Female: ovaries.

What does phenotypic sex include?

Reproductive tracts, accessory glands, and external genitalia.

How many pairs of autosomes do humans have?

22 pairs.

What is the 23rd pair of chromosomes called?

The sex chromosomes.

How many genes does the X chromosome contain?

About 900 genes.

How many functional X chromosomes are required for survival?

At least one; zero X chromosomes is fatal.

How many genes does the Y chromosome contain?

About 55 genes.

What is the function of the SRY gene?

Codes for the sex-determining region Y, leading to male development.

Is the Y chromosome required for survival?

No.

What are common traits of individuals with XYY?

May be taller than average; may have delayed language development.

Does hormone exposure affect gonadal development?

No—gonadal development is gene-dependent only.

What happens when one or more Y chromosomes are present?

Testes develop.

What happens when no Y chromosome is present?

Ovaries develop.

Until what week are gonads undifferentiated (bipotential)?

Until the 6th week of development.

Which factors promote ovary development?

RSPO1, β-catenin, and WNT4 (they block SOX9).

Which factors promote testis development?

SRY activates SOX9, which blocks RSPO1, β-catenin, and WNT4.

Are RSPO1, WNT4, β-catenin, and SOX9 autosomal factors?

Yes, they are autosomal and present in every cell.

What reproductive duct structures are present before sexual differentiation?

Both Wolffian (male) and Mullerian (female) duct progenitors.

What does the Mullerian duct develop into?

Oviduct (uterine tube), uterus, cervix, and upper vagina.

What does the Wolffian duct develop into?

Epididymis, vas deferens, and seminal vesicle.

What determines phenotypic sex?

Hormones that shape internal reproductive tracts and external genitalia.

Which hormones do ovaries secrete?

Estrogen and progesterone.

Which organs does estrogen influence during development?

Breasts, uterus, vagina, and ovaries.

Which hormones do testes secrete?

Testosterone and anti-Mullerian hormone (AMH).

What converts testosterone into DHT?

The enzyme 5-α-reductase in target tissues.

How potent is DHT compared to testosterone?

More potent; binds the same receptor with greater strength.

What portion of circulating testosterone becomes DHT?

About 10%.

What is estradiol?

The most potent form of estrogen.

How is most estradiol formed?

About 70% is formed from circulating testosterone via aromatase.

How much estradiol is found in adult males?

Small amounts, about 2 ng/dL.

What is the default developmental pathway for external genitalia?

Feminization.

What structures form by default (without hormonal influence)?

Vaginal opening, labia majora/minora, and clitoris.

What is required for masculinization of external genitalia?

Dihydrotestosterone (DHT).

Which structures develop under the influence of DHT?

Penis, urethra, and scrotum.

What is the chromosomal sex in Turner Syndrome?

XO

What is the gonadal sex in Turner Syndrome?

Ovaries

What is the internal phenotypic sex in Turner Syndrome?

Mullerian ducts develop (no AMH or testosterone)

What is the external phenotypic sex in Turner Syndrome?

Feminization (no DHT)

What is the chromosomal sex in Klinefelter Syndrome?

XXY

What is the gonadal sex in Klinefelter Syndrome?

Testes

What is the internal phenotypic sex in Klinefelter Syndrome?

Wolffian ducts (AMH + testosterone)

What is the external phenotypic sex in Klinefelter Syndrome?

Masculinization (DHT)

What causes Androgen Insensitivity Syndrome (AIS)?

Mutation in androgen receptors preventing response to testosterone

What is the chromosomal sex in AIS?

XY

What is the gonadal sex in AIS?

Testes

What is the internal phenotypic sex in Androgen Insensitivity Syndrome (AIS)?

No Wolffian or Müllerian ducts (AMH works; testosterone/DHT cannot)

What is the external phenotypic sex in AIS?

Feminization (androgens cannot bind receptors)

What causes Congenital Adrenal Hyperplasia (CAH)?

Excess testosterone production from the adrenal gland

What is the chromosomal sex in CAH?

XX

What is the gonadal sex in CAH?

Ovaries

What is the internal phenotypic sex in CAH?

Both Wolffian and Müllerian ducts (testosterone present but no AMH)

What is the external phenotypic sex in CAH?

Feminization with partial masculinization (testosterone lower than testes levels)