Sex Differentiation

1. SEXUAL
DIFFERENTIATI
ON
Dr P V Logenthiran

2. Objectives
 At the end of the lecture, student should be able
to:
 Define genetic male and female
 Describe the normal sexual differentiation
 Describe the regulation of the development of internal
and external genitalia
 Describe the role of testosterone and Mullerian
Inhibiting Substance in sexual differentiation
 Describe abnormal sexual differentiation

3. Sex Determination
 Genetic Sex
 Genetic male
 Genetic female
 Gonadal Sex
 Testis
 Ovary
 Phenotypic sex
 Male external genitalia
 Female external genitalia

4. Sex Determination
 Genetically determined by two chromosomes:
 Sex Chromosomes
 In humans they are called X chromosome & Y
chromosome
 Sex determination primarily depends on presence or
absence of Y chromosome
 Y chromosome is necessary for the production of
testis
 Testis producing gene product – SRY
 SRY
 DNA binding regulatory protein
 It bends the DNA and act as a transcription factor that
initiates transcription of a cascade of genes necessary
for testicular determination (including gene for MIS)

5.  The gene for SRY is located:
 Tip of the short arm of the Y chromosome
 Each normal ovum contains a single X chromosome
 Half of the normal sperms carry X chromosome and
other half carry Y chromosome
 Sperm containing Y chromosome fuses with Ovum
 Genetic male embryo is produced 46, XY
 Sperm containing X chromosome fuses with Ovum
 Genetic female embryo is produced 46, XX

6. Development of Gonads
 On either side of the embryo, a primitive gonad
arises from the genital ridge
 Develops as Cortex & Medulla
 Initially ambi-sexual (up to 6 weeks)
 In genetic males:
 Medulla develops in to testis (7 – 8 weeks)
 Cortex regresses
 Leydig cells & Sertoli cells appear
 Testosterone & MIS are secreted (by Leydig & Sertoli
cells respectively)

7.  In genetic females:
 Cortex develops into Ovary
 Medulla regresses
 Embryonic ovary does not secrete hormones
 Maternal hormonal treatment has no influence on
Gonadal development

9. Internal genitalia
 Embryo around 7 weeks has both male & female
genital ducts
 Mesonephric (Wolffian) duct – male genital duct
 Para-mesonephric (Mullerian) duct – female genital duct
 When embryo has a functional testis:
 Leydig cells secrete Testosterone
 Fosters the development of Wolffian duct system
 Sertoli cells secrete MIS
 Inhibits development of Mullerian duct system
 Wolffian duct system develops into:
 Epididymis / Vas deferens / Seminal vessicles

10.  In embryos with Ovary:
 No testosterone
 Wolffian duct system regresses
 No MIS
 Allows development of Mullerian duct system
 Mullerian duct system develops into:
 Fallopian tubes / Uterus / Cervix / Upper vagina

11. External genitalia
 Until 8 weeks in embryonic life, the external genitalia
are bi-potential
 In the presence of testosterone:
 Testosterone is converted to DHT by 5-alpha reductase
 DHT promotes the development of bi-potential external
genitalia to become Male External Genitalia
 Enlargement of genital tubercle – Penis
 Fusion of urethral fold over uro-genital sinus – Penile
urethra
 Fusion of labio-scrotal swelling – Scrotum

12.  In females:
 No Testosterone
 No DHT
 Therefore the bi-potential external genitalia
differentiates in to female external genitalia
 Genital tubercle remains – Clitoris
 Non fusion of uro genital sinus – Lower vagina &
urethra (vestibule)
 Non fusion of urethral folds – Labia minora
 Non fusion of labio scrotal swelling – Labia majora

13. Aberrant Sexual Differentiation
 Caused by:
 Chromosomal abnormalities
 Hormonal abnormalities
 Chromosomal Abnormalities:
 Due to non-disjunction of sex chromosomes during the
first meiotic division – usual cause
 Non disjunction during second meiotic division – more
complex abnormalities
 Non disjunction during mitotic division after fertilization
– Mosaicism – True Hermaphrodite – Individual with
ovaries & testis
 Transposition of parts of chromosomes – Males with
XX karyotype and Females with XY karyotype

14. Non Disjunction of Sex
Chromosomes
44
XX
22 0 22
XX
44
X0
44 XXX
22 X 22 X
Ovum
Zygote
Sperm

15. Non Disjunction of Sex
Chromosomes
44
XX
22 0 22
XX
44
Y0
44 XXY
22 Y 22 Y
Ovum
Zygote
Sperm

16.  Hormonal abnormalities:
 Female pseudo-hermaphroditism
 Exposure to exogenous androgens during development (8
– 13 weeks)
 Congenital Adrenal Hyperplasia
 Female type gonads and internal genitalia but male external
genitalia
 Male pseudo-hermaphroditism
 Defective testicular development
 Androgen insensitivity syndrome
 5-alpha reductase deficience
 Androgen receptor mutation
 17-alpha hydroxylase deficiency

17. Thank you