Flashcards in Reproduction Malformation Deck (14):
Name the three major branch points in determining the sex of a developing fetus.
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
What two types of cells are required for gonadal development and what tissues do they develop from?
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
What elements are required for the development of male internal genitalia?
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)
What elements are required for the development of female internal genitalia?
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
What hormone is responsible for the development of male external?
testosterone is converted to DHT (dihydrotestosterone) in peripheral tissues and causes
genital tubercle -> penis
labioscrotal folds -> scrotum
urogenital folds -> penile urethra
What hormone is responsible for the development of female external genitalia?
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
Describe the syndrome of congenital gonadotrophin-releasing hormone deficiency (cause and symptoms)
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
Describe the abnormal gonadal development in Turner Syndrome.
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
Describe the anatomical abnormalities associated with Mullerian agenesis.
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
Describe the presentation of outflow obstruction caused by imperforate hymen or transverse vaginal septum
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
What are the primary anatomical abnormalities seen in an undervirilized XY patient?
androgen insensitivity syndrome due to inactive receptors, results in anatomic sex abnormalities:
absent male internal genialia (Wolfian duct)
absent female internal genitalia (Normal AMH)
presence of female external genitalia (no DHT receptor)
no virilization (receptor defect)
no pubic hair (receptor defect)
normal breast development (peripheral conversion of testosterone to estrogen)
amenorrhea (no uterus due to AMH)
How are females with a blind vagina differentiated form undervirilization of XY male? (think secondary sex characteristics, chromosomes, hormone levels, external phenotype)
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
Describe the pathophysiology of CAH and how classic CAH causes virilization of XX. How does it present in boys and girls?
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