Sex Determination Flashcards
What is an embryo described as before sex determination?
Bipotent or sexually indifferent
When does sex determination begin?
<7 weeks gonadal ridges could develop into testes or ovaries
> 7 weeks gender development as determined by sex chromosomes
Normal male sex determination?
1) Sry gene activates cascade of genes on autosomes and y involved in male development
2) testes development is initiated
3) testes release testosterone - leading to normal male development
Normal female development >7 weeks
Not just absence of SRY- 2 x’s required for normal female development
Gene involved in secondary dif- important for development of kidneysa and gonads?
WT1:11p13
Location and role of SF1?
9q33
Steriodogenic factor 1
Gene that is a transcription factor for gonadal development?
LHX9: 1q31-32
Role and location of sox9?
17q24-25 required for male and female development. Mutations can lead to sex reversal
Location and role of DAX1
Xq21- dosag sensitive sex reversal adrenal hyperplasia Critical region
What is sex reversal?
When phenotypic sex and chromosomal sex differ
What are the two causes of male sex reversal?
80% have unbalanced X-Y translocation so Y material (including SRY)on distal X
20% have no SRY and partial male/ambiguous sexual development
Causes of sex reversal in females?
XY females usually carry a copy of the SRY gene and either
A) SWYER SYNDROME- a genetic mutation in Sry or other genes in development cascade
B) androgen insensitivity syndrome - sry working but have failure of response of an androgen receptor
Symptoms of swyer syndrome/pure gonadal dysgenesis?
Streak gonads (mainly fibrous tissue) Female external genitalia Failure of puberty 30% risk of developing gonadoblastoma (remove gonads in 1st decade of life)
Symptoms of complete androgen insensitivity/ testicular feminisation?
Female external genitalia ; short/absent vagina At puberty development of breasts Amenorrhea Intra abdominal testes 2-5% risk of gonadoblastoma
Examples of androgen resistance syndromes?
5alpha-reductase
17alpha hydroxylase deficiency
Symptoms of androgen resistance syndromes ?
46, XY karyotype
Bilateral testes and normal secretion of testosterone
Female external genetalia but virilisation of external genetalia at puberty
Male breasts
Reduced spermatogenesis
What causes congenital adrenal hyperplasia (CAH)?
Enzyme deficiencies affecting steroidogenesis
Classic = 21- hydroxylase deficiency
In utero- what’s the phenotype of XX and XY with CAH?
XX- masculinisation of external genetalia
XY- normal genetalia
How do u treat CAH pregnancies? What’s the risk if untreated?
Treat with DEXAMETHASONE in utero and with hormones after birth
If untreated = salt-wasters. Can die in a few weeks
How does autosomal sex reversal occur? Give an example?
Autosomal imbalance in regions carrying other genes in the male determining cascade- e.g deletion/ unbalanced translocation of 9q33 (SF1)
Phenotype of autosomal sex reversal?
Female phenotype
Usually also mentally retarded and dysmorphic due to unbalanced karyotype
What is associated with a 9p24 deletion?
Contains SRXY genes - sex reversal
Deletions of 10q26.1
Genital abnormalities - most common cryptorchidism (testes undescended)
What syndromes associated with 11p13 deletion?
Gene= WT1- associated with Wilma tumour, WAGR, Frasier syndrome, and Denny - crash syndrome
Phenotype of translocation involving 17q24.3-q25.1
Sox9 gene
Compomelic dysplasia - skeletal abnormalities and death!!
What could cause an XY female?
Duplication of Xp21 (DAX1 gene) - double dose of DAX1 disrupts testis development
What is hermaphroditism?
Gonads comprise both ovarian and testicular elements
Ambiguous external genetialia
What are the most common causes of hermaphroditism?
Most common. 46, XX (no Y chromosome)
Occasionally chimerism 46 xx/46 xy
What are pseudohermaphrodites?
Have ambiguous genetalia and gonads of either
1) ovarian elements only = female hermaphrodite
2) testicular elements only = male pseudohermaphrodite
