Disorders of sexual development

Question 1

define: chimera

Answer 1

• mixture of genetically different cells which originate from different zygotes
• 2 embryos develop as single individual
• double fertilization of oocyte

Question 2

types of chimeras

Answer 2

• XX/XY –> easily detectable

- XX/XX or XY/XY –> usually no abnormal sexual differentiation

Question 3

define: mosaic

Answer 3

• 2 or more cell lines from a single zygote
• from a lost or added chromosome (disorder of non-disjunction in mitosis)
• most likely in sex chromosomes

Question 4

true hermaphrodite

Answer 4

• has both ovarian and testicular tissue

- any combination of ovaries and testes

Question 5

2 situations of true hermaphroditism

Answer 5

• timing of expression of SRY is shifted (later) so it overlaps with the expression of the ovarian developing program
• male and female supporting cells are simultaneously present (XX/XY chimeras and XY/XO mosaics)

Question 6

pseudohermaphrodite

Answer 6

• abnormality of phenotypic sex
• chromosomal and gonadal sex are the same, but the phenotype of the internal and/or external genitalia show some features of the opposite sex

Question 7

male pseudohermaphrodite

Answer 7

XY chromosomes and testes but female characteristics of internal or external genitalia

Question 8

female pseudohermaphrodite

Answer 8

XX chromosomes and ovaries but masculinized genitalia –> rare

Question 9

sex-reversal

Answer 9

• both gonadal and phenotypic sex agree but are at odds with chromosomal sex
• true hermaphrodites may occur

Question 10

XX sex-reversed males

Answer 10

• have testes and are phenotypically male though sterile (XX germ cells can’t survive in testes)
• due to translocation of SRY to X or an autosome

Question 11

XY sex-reversed females

Answer 11

• female phenotype and ovaries but chromosomally XY
• ovaries degenerate to streak gonads
• due to deletion of Sry

Question 12

what are androgen based disorders

Answer 12

genetic defects that decrease androgen action in genetic males or increase it in genetic females

Question 13

what type of gene is androgen receptor the product of

Answer 13

x-linked gene

Question 14

what does complete deficiency (no AR) lead to

Answer 14

testicular feminization/complete androgen insensitivity (CAIS) –> XY, have testicles (inguinally) but phenotypically taller than average females

Question 15

hormones involved with CAIS and effects

Answer 15

• not T-AR –> wolffian duct regression (have T, but it can’t work)
• -no DHT-AR –> female external genitalia (have DHT, but it can’t work)
• normal MIS –> mullerian duct regression (have MIS and receptor, so it works)

Question 16

partial androgen insensitivity syndrome

Answer 16

partial inactivation –> variable phenotype)

Question 17

5alpha-reductase defects

Answer 17

• have T but can’t make DHT
• normal androgen receptor –> T can function normally
• XY, bilateral testes, normal wolffian structures that en in blind vagina, external female genitalia, female brain sex

Question 18

what is persistent mullerian duct syndrome in males (PMDS)

Answer 18

• results in male pseudohermaphroditism
• relatively normal males that may have cryptorchidism but also a uterus and oviducts
• from either MIS deficiency or end-organ unresponsiveness
• only homozygous males affected

Question 19

cryptorchidism in patients with PMDS

Answer 19

• testis tightly linked to retained oviducts

- testes descend, dragging the oviducts and portion of the uterus along into inguinal canal

Question 20

what deos exposure of female fetuses to MIS during early embryogenesis cause

Answer 20

regression or agenesis of Mullerian structures and later potentially “endocrine sex reversal” of the ovaries (because MIS inhibits aromatase)

Question 21

what happens to immature ovaries exposed to MIS

Answer 21

reduced aromatase activity and hence produce more testosterone (builds up because they can’t convert it to estrogen)

Question 22

cause of turner syndrome

Answer 22

usually paternal (the result of defective sperm –> errors in meiosis or mitosis)

Question 23

cause of kleinfelter’s syndrome

Answer 23

defects arise equally from mother and father due to errors in meiosis

Question 24

freemartinism info

Answer 24

• requires vascular anastomosis of chorioallantoic vessels between twin cattle placentas
• indifferent gonad of male develops first, produce MIS
• female gonads inhibited by MIS –> mullerian regression

Question 25

freemartinism and female twin

Answer 25

rudimentary ovary, small vulva, short vagina –> sex-reversed gonads produce testosterone due to inhibition of aromatase enzyme

Question 26

freemartinism and male twin

Answer 26

reduced fertility and libido

Question 27

polled/intersex syndrome info in goats

Answer 27

• european dairy breeds
• sex reversed females (XX with testes)
• look female at birth, become more masculine after puberty
• Sry negative but have deletion from chromosome 1 (PIS -/-) –> recessive

Question 28

how does polled intersex syndrome work

Answer 28

• normal XX females: PIS is normal promoter region that upregulates PISRT1 –> inhibits SOX9 (testis formation)
• PISRT1 is anti-gestis gene
• affected animal: deletions mean SOX9 not inhibited –> testicle forms
• homozygous males are sterile

Question 29

sex-reversed horses

Answer 29

• XX: sry negatve (downstream issue)

- XY: sry negatve (lack of sry was problem)

Question 30

hypospadias in dogs

Answer 30

• partial failure of fusion of the urogenital folds
• urethra does not open at the end of the glans penis but further back
• form of male pseudohermaphroditism
• due to inadequate T, inadequate activity of 5alpha-reductase, or defects in downstream genes

Question 31

XX sex reversal in dogs

Answer 31

• chromosomally female but have bilateral testes, male tracts –> male externally
• XX hermaphrodites
• cocker spaniels

Question 32

persistent mullerian duct syndrome in dogs

Answer 32

• form of male pseudohermaphroditism
• XY with bilateral testes but half are cryptorchids
• full mullerian strutures
• miniature schnauzers
• autosomal recessive trait

Question 33

tortoiseshell cats

Answer 33

• black and tabby are autosomal, orange is on X (O is dominant)
• males with O are always orange, females can have one O and one black –> X inactivation –> torties