Reproduction Malformation

Question 1

Name the three major branch points in determining the sex of a developing fetus.

Answer 1

1) chromosomal sex
2) development of testes or ovary based on genes
3) hormones produced by tests direct development of internal and external genitalia

++sex of rearing

Question 2

What two types of cells are required for gonadal development and what tissues do they develop from?

Answer 2

somatic cells- develop from epithelium of peritoneum and undifferentiated gonadal ridge

primordial germ cells- are formed from dorsal endoderm in the base of the alantois (outside the embryo);

PGC migrate to reach the genital ridges and mix with somatic cells to form undifferentiated gonads

all at 4 weeks

Question 3

What elements are required for the development of male internal genitalia?

Answer 3

SRY genes present on the Y chromosome causes development of tests from undifferentiated gonad

testes secrete AMH (involution of the Mullein duct) and testosterone (promotes Wolffian duct differentiation)

Question 4

What elements are required for the development of female internal genitalia?

Answer 4

absence of SRY gene and expression of FOXL2 gene cause development of undifferentiated gonad into an ovary

absence of AMH causes differentiation of Mullein duct (into uterus, fallopian tubes and upper ⅓ of vagina)

absence of testosterone cause involution of Wolffian duct

Question 5

What hormone is responsible for the development of male external?

Answer 5

testosterone is converted to DHT (dihydrotestosterone) in peripheral tissues and causes
genital tubercle -> penis
labioscrotal folds -> scrotum
urogenital folds -> penile urethra

Question 6

What hormone is responsible for the development of female external genitalia?

Answer 6

no hormone is responsible, the absence of dihydrotestosterone leads to female phenotype

genital tubercle -> clitoris
labioscrotal folds -> labia majora
folds of the urogenital sinus -> labia minor, urogenital sinus becomes the urethra and lower vagina

Question 7

Describe the syndrome of congenital gonadotrophin-releasing hormone deficiency (cause and symptoms)

Answer 7

Kallman’s Syndrome due to defective migration of GnRH containing neurons form the olfactory nasal epithelium to the hypothalamus (KAL1 and KAL2 genes)

inadequate LH/FSH secretion and the absence of estrogen production lead to delayed puberty, amenorrhea; associated anosmia

Question 8

Describe the abnormal gonadal development in Turner Syndrome.

Answer 8

genotypes can include
45X - primary ovarian failure
46 XX gonadal dysgenesis
46 XY gonadal dysgenesis (rare)

gonads are replaced with fibrous tissue leading to high FSH/LH and low estradiol, primary amenorrhea; characteristic streak ovaries and abnormal karyotype (used in dx.)

associated: short stature, shield like chest, aortic coarctation and bicuspid aortic valve

presence of Y chromosome requires gonadectomy

Question 9

Describe the anatomical abnormalities associated with Mullerian agenesis.

Answer 9

presents with normal female phenotype with absence of the uterus (ONLY), leading to lack of menses

ovaries are developed, normal puberty due to gonad synthesis of hormones

Question 10

Describe the presentation of outflow obstruction caused by imperforate hymen or transverse vaginal septum

Answer 10

presents with hematocolpos (bluish distention of the vulva) and monthly cyclic pain; represents a higher risk for endometriosus because menstrual fluid leaks into the pelvic area

all other internal and external genitalia develop normally

Question 11

What are the primary anatomical abnormalities seen in an undervirilized XY patient?

Answer 11

androgen insensitivity syndrome due to inactive receptors, results in anatomic sex abnormalities:
At birth:
undescended testis
absent male internal genialia (Wolfian duct)
absent female internal genitalia (Normal AMH)
presence of female external genitalia (no DHT receptor)

At puberty:
no virilization (receptor defect)
no pubic hair (receptor defect)
normal breast development (peripheral conversion of testosterone to estrogen)
amenorrhea (no uterus due to AMH)

Question 12

How are females with a blind vagina differentiated form undervirilization of XY male? (think secondary sex characteristics, chromosomes, hormone levels, external phenotype)

Answer 12

androgen insensitive syndrome differences:
pubic hair will not develop (no DHT receptors)
testosterone levels are only high in AIS

chromosomes and gonads present will be different

Question 13

Describe the pathophysiology of CAH and how classic CAH causes virilization of XX. How does it present in boys and girls?

Answer 13

impaired 21-hydroxylase activity leads to impaired cortisol production and precursors are shunted to androgen production

this will present with ambiguous external genitalia in girls and adrenal crisis in males (newborn screen helps to prevent) ** al require treatment for hypoglycemia and hyponatremia

Question 14

What is the acceptable way to refer to a patient previous called a true hermaphrodite?

Answer 14

both ovarian and testicular tissue is present