Sex Determination and Genitalia Development (Lec 11/12) Flashcards
Sex Determination: Genetics
In humans, sex is determined at fertilization by Y chromosome:
XY (heterogametic) = male
XX (homogametic) = female
Y Chromosome
Sex Determining Region (SRY) gene codes for Testes Determining Factor (TDF) -> TDF directs embryonic gonads to develop into testes -> secretion of Testosterone and Mullerian Inhibiting Substance
Crossing Over in Male Meiosis
Tips of X and Y pair in Meiosis in Psuedo-autosomal regions (PAR1 and PAR2). Cross over of PAR1 essential for proper segregation of chromosomes. Non-recombining region of Y (NRY) unique to Y chromosome and gets passed on without crossing over
Compensation Mechanism
Inactivation of all X chromosome through silencing. X-inactive specific transcript (Xist) causes not all genes to be silenced.
X-Inactivation
In females, 1 X-chromosome randomly inactivated around 16 days post fertilization. The inactive X forms a discrete body within the nucleus (Barr Body).
Development of Gonads - Indifferent Gonads
Initial development of gonads occur during 5th week. Primordial germ cells originate in the endodermal epithelium of the yolk sack and migrate along the mesentry of the hindgut to the Gonadal Ridge (precursor of gonads)
Indifferent Gonads
During early stages of fetal development, 2 duct systems arise: Wolffian and Mullerian ducts. Initially, both sexes have both ducts.
Wolffian Ducts (Mesonephric Ducts)
Progenitors of the upper male genital tract
Mullerian Ducts (Paramesonephric Ducts)
Progenitors of the upper female genital tract
Pre-Week 7: Indifferent Gonads
Gonads of the 2 sexes are identical in appearance. Indifferent gonads consist of an outer cortex and inner medulla
Post-Week 8: Early Ovaries and Testes
Gonads changed to male phenotype if genes on Y chromosome are expressed.
Females: ovaries develop from the cortex of the indifferent gonad, medulla regresses
Males: Testes develop from medulla of the indifferent gonad, cortex regresses
The Fate of Wolffian Ducts
With TDF:
- > Testes develop from the medulla, cortex regresses
- > Testes produce Testosterone and Mullerian-inhibiting factor (MIF)
Testosterone Present:
-> Wolffian Ducts turn into male reproductive system
MIF Present:
-> Mullerian ducts regress
The Fate of Mullerian Ducts
Without TDF:
-> Ovaries develop from the cortex, medulla regresses
If NO Testosterone and MIF:
- > Default female development occurs
- > Mullerian ducts turn into female reproductive system
- > Wolffian ducts degenerate
Development of the Gonads
Differentiation of Ovaries or Testes from the bipotential gonadal ridge is fully achieved by week 13-14 (fetal life)
Males: Medullary cords develop, no Cortical cords
Females: Cortical cords develop, no Medullary cords
Development of External Genitalia
Pre-week 8: sex neutral, undifferentiated external genitalia
Post-week 8: distinguishing sexual features begin to appear
12th week: external genitalia fully differentiated
Differentiation of Male External Genitalia
- > Fetal Leydig cells produce testosterone
- > Enzyme 5α-reductase-2 converts testosterone into dihydrotestosterone (DHT)
- > Complete masculinisation of external genitalia by DHT by the 14th week
Descent of Testes
Occurs after 3rd month of pregnancy. Testes transferred from lumbar area of body into the future scrotum through the Inguinal Canal. Transfer due to a combination of growth processes and hormonal influences (androgens)
Differentiation of Female External Genitalia
Primary female sexual differentiation occurs slowly in the fetus and does not depend on hormones. Growth of primordial phallus gradually ceases and becomes Clitoris, Labia majora are homologous with male scrotum
Disorders of Sex Development (DSD)
Conditions resulting in discordance between genetic, gonadal, or anatomic sex (internal & external structures)
Ambiguous Genitalia
Rare condition where infant’s genital phenotype do not appear to be male or female. Genitals either incompletely developed or both sexes present
Sex Reversal Studies: SRY Translocation
SRY locus translocated onto X chromosome during crossing over. If sperm containing SRY-containing X chromosome fertilises ooctye -> Karyotype of individual will not match phenotypic expression
Swayer Syndrome
Affects 1:80,000. 46, XY
- Y chromosome present, genetically male
- However, Y chromosome does not have SRY gene, therefore female reproductive tract exists
XX Male Syndrome
Affects 1:20,000. 46, XX
- No Y chromosome, genetically female
- SRY translocated onto X chromosome which causes formation of both Ovaries and Testes in same individual
Androgen Insensitivity Syndrome (AIS)
Affects 2-5:100,000. 46, XY
- Functional SRY gene, TDF expressed, however due to Androgen insensitivity, female characteristics occur
- Testosterone produced from testes but target cells lack receptors for Androgens, no masculinizing effect
Testosterone Deficiency
46, XY
Functional SRY gene, TDF produced, female characteristics due to:
- Leydig cells in testes not secreting testosterone
- Internal structures male, external genitalia female
5α-reductase Deficiency
46, XY
Functional SRY gene -> TDF expressed, female characteristics due to:
- 5α-reductase Deficiency not producing enough DHT
- Male gonads with ambiguous genitalia
True Cryptochidism
Absence of one or both testes from the scrotum.
- Spermatogenesis is greatly influenced by temp
- > risk of infertility, testicular torsion and cancers
Sex Change
Female sexual characteristics are substituted for Males, or vice versa.
Protandrous Hermaphrodites
Organisms that are born male but at some point in life change sexes and become female
Protogyous Hermaphrodites
Organisms that are born female but at some point in life change sexes and become male
Sex Determination in Animals
Drosophilia Melanogaster: determined by number of X’s
- Male: XY, XO (sterile)
- Female: XX, XXY
Arachnids: 1 sex chromosome (X)
- Male: XO
- Female: XX
Birds: Designated Z & W (sex-determining) chromosomes
- Male: homogametic ZZ
- Female: heterogametic ZW
