Abnormal reproductive development Flashcards
In male fetuses, ______ causes the undifferentiated fetal gonad to develop into testes
SRY gene on Y chromosome
absence of SRY in females- gonad develops into ovaries
The fetal testes secrete _____ and _____
testosterone
Contrast the effects of AMH vs testosterone in male fetuses
AMH causes regression of the Mullerian duct
testosterone promotes Wolffian duct differentiation
Describe early reproductive tract development in female fetuses
- absence of testosterone causes Wolffian duct regression
- lack of AMH allows for Mullerian duct differentiation into fallopian tubes, uterus, upper 2/3 of vagina
In the absence of ___________, the genital tubercle becomes the clitoris, the urogenital sinus remains open to form the labia minora, the labioscrotal folds form the labia majora, and the urogenital sinus becomes the urethra and lower vagina.
dihydrotestosterone
List three basic causes of sexual ambiguity
- Inappropriate virilization of a genetic female due to exposure to excess androgens.
- Under-masculinization of a genetic male due to reduced androgen production or impaired androgen responsiveness of target tissues.
- Presence of both ovarian and testicular tissue.
In female fetuses, the absence of SRY gene and expression of ______ gene causes the undifferentiated gonad to form an ovary
FOXL2
_______ is caused by defective migration of the GnRH containing neurons from the olfactory nasal epithelium to the hypothalamus
Kallmann’s Syndrome
usually KAL1, KAL2 genes
List key distinguishing features of Kallmann’s syndrome in females
Ovarian dysfunction from hypothalamic source
- low LH/FSH
- absence of estrogen production
- delayed puberty, amenorrhea
- ansomnia
In ______, amenorrhea occurs because the ovaries are replaced with fibrous tissue and do not produce sufficient estrogen
gonadal dysgenesis
In all causes of gonadal dysgenesis, FSH levels are (high/low)
high- absence of estrogens from ovaries= no negative feedback of estrogen on FSH
What is the most common cause of gonadal dysgenesis?
Turner syndrome
What treatment is necessary in cases of gonadal dysgenesis with 46, XY karyotype?
gonadectomy- Y chromosome gives higher risk of gonadal tumors such as gonadoblastoma
List key features of Mullerian agenesis?
female phenotype absence of uterus ovaries are present lower 1/3 of vagina is developed (urogenital sinus origin) but upper 2/3 is missing (Mullerian duct origin) hormone levels normal amenorrhea
_________ and ________ are characterized by cyclic pelvic pain and a perirectal mass from sequestration of blood in the vagina (hematocolpos).
Transverse vaginal septum, imperforate hymen
What are the expected hormone levels in anatomic abnormalities of the female reproductive tract (transverse vaginal septum, Mullerian agenesis)
normal LH, FSH, estradiol for pubertal stage
normal pubertal development- breast development, pubic hair
primary amenorrhea
List key findings in androgen insensitivity syndrome
- 46, XY with female phenotype due to lack of sensitivity to androgens- bilateral undescended testes
- blind vaginal pouch, absent Mullerian- derived structures
- breast development- aromatization to estrogen at breast
- testosterone levels in normal range for adult males
- PUBIC HAIR ABSENT- depends on androgen action at receptors
List the genital structures that are present/ absent in AIS and why
Absent male internal genitalia (No testosterone receptor)
Absent male external genitalia (No DHT receptor)
Absent female internal genitalia (Normal AMH)
Presence of female external genitalia (No DHT receptor)
List similarities and differences between Mullerian agenesis and AIS
similarities: both have no uterus, no internal male genitalia, normal breast development in puberty, development of lower 1/3 of vagina
differences
- Mullerian agenesis does have pubic hair
- AIS= 46, XY; Mullerian agenesis= 46, XX
- Mullerian agenesis- testosterone level is normal for females; AIS- testosterone level in adult male range
Congenital adrenal hyperplasia is due do a deficiency of _____ which is responsible for:
21-hydroxylase
conversion of cholesterol to cortisol
In severe impairment of 21-hydroxylase, levels of CRH/ ACTH are (high/ low)
high, due to lack of cortisol negative feedback
How to newborn girls with CAH present?
ambiguous genitalia, present Mullerian structures and ovaries
What is the treatment for classic CAH?
glucocorticoids, suppress HPA axis from making excess androgens
