Sexual Differentiation in utero

Factor responsible for differentiation :

1. Effect of sex chromosome on differentiation of gonads 2. Proper function of differentiated tests. 3. Response of end organ to testicular activity.

Sex Chromosomes
XY
Abnormal function

XX
Female
5a reduction

Testis
Normal function Anti-Mullerian hormone (sertoli cells) (-) Mullerian duct

Ovary
DHT
(+) External genitalia

Testosterone Leydig cells (+) Wolffian duct

Epidedimis Vas Seminal vesicle

No Uterus, Tubes
& vagina

Male

Abnormal Sexual Differentiation

1. Abnormal chromosomes
2. True hermaphrodism (ovarian + testicular tissue) 3. Inability of testosterone production anatomical failure complete failure of testosterone production

Abnormal Sexual Differentiation

4. Inability AMH production
5. End organ insensitivity
5a reeducates deficiency Failure of testosterone to bind to receptor (androgen/insensitivity).

6. Congenital adrenal hyperplasia

Presentation in clinical practice

I. Musculanized female (female inter sex) Congenital adrenal hyperplasia Drug intake (danazol methyl testosterone) II. Under musculanized male (Male inter sex) Anatomical testicular failure End organ insensitivity Androgen insensitivity 5a reductase. III.True hermaphrodite

Congenital Adrenal Hyperplasia

Definition :
Masculization of external genitalia of a genetic female due to androgen stimulation from other source than testis.

Pituitary
ACTH
Masculinization of external genitalia

(-)

Salt & water loss

Aldosterone

Cholesterol

Progesterone

21 hydroxylase

X
Cortisol

17 hydroxylase

17a hydroxy 21 hydroxylase X progesterone Testosterone

Hypertrophy of clitoris Fusion of labia majora Labia majora skin is thick resembling scrotum

Treatment :
Cortisol to suppress ACTH. Control salt and water loss. Surgical correction by removing clitoris and incision of labial folds.

Differentiation between male inter sex and true hermaphrodite

1. Laparoscopy and gonadal biopsy. 2. Sex if rearing is according to suitability of external genitalia to sexual life.

Male Inter Sex

Anatomical testicular failure

XY
Isochromosomes Mosaic

Testis
Poorly differentiated

No
AMH Uterus Tubes vagina

No
Testosterone No stimulation No DHT to wolfian duct No seminal vesicle No epidimis No vas No masculinization
of external genitalia

Sex of rearing is female.

Gonadectomy (30% risk of malignancy).

Puberty E + P replacement therapy to develop secondary sexual character and to have menstruation. Patients will remain infertile since there is no ovary.

Male Inter Sex

5a reductase defficiency

XY
AMH
Uterus Tubes vagina

Testis Testosterone
Epidimis Vas Seminal vesicle

No 5a reductase No

No

DHT No masculinization
of external genitalia

Sex of rearing is female.

Removal of testis before puberty because if left till puberty patient may wish to change from female to male.

Male Inter Sex

Androgen In sensitivity (receptor defect)

XY
AMH
Uterus Tubes vagina
No

Testis Testosterone
No

No

Epidimis Vas Seminal vesicle

DHT No masculinization
of external genitalia

Assay of testosterone is normal however is unable to exert its effect due to defficency in bonding to receptor of target organ. Presentation at puberty with primary amenorrhea, no pubic hair. Sex of rearing is female Removal of testis (5% cancer).

True hermaphrodite
Testis and ovary are present in the same patient or as ovotestis in one or both sides. Diagnosis is by gonadal biopsy. Surgery is needed to remove unsuitable genitalia and gonads before puberty. Since one of the gonads may be stimulated leading to masculinization of female of feminization of a male and this will put patient is severe emotional conflict.

Abnormal Chromosomes
XX O X Y

XXX
Super female

XXY
Kleinfelter

XO
Turner

YO
Incompatible with life

Data show design by : Dr. El-Sayed Amr - (012) 3106023