Chromosomal Sex

1
Chromosomal Sex

• sex is determined by chromosomes at fertilization
• XX female, XY male
• X chromosome contains many genes necessary for
  survival
• Y chromosome contains very few genes
• important gene on Y chromosome SRY gene
• SRY sex-determining region on the Y chromosome

2
Sexually indifferent stage

• initially, gonads, sex accessory ducts and
  external genitalia are identical for both sexes

3
Genital ridges

• appear as gonadal ridges
• near midline at back of abdominal cavity
• two regions outer cortex, inner medulla
• contain no germ cells
• lasts from 5th to 7th week

4
Undifferentiated Ducts

• Wolffian ducts (will go on to form male accessory
  structures)
• Mullerian ducts (will go on to form female
  accessory structures)

5
Indifferent external genitalia

• genital tubercle (will form penis or clitoris)
• urogenital folds (will form part of penis or
  labia minora)
• labioscrotal swelling (will form scrotum or labia
  majora)

6
Primordial germ cells

• originate in yolk sac
• migrate to region of gonadal ridges (by 5 weeks)
• proliferate en route
• in females, germ cells colonize cortex and
  medulla degenerates
• in males, germ cells colonize medulla and cortex
  degenerates

7
Female gonadal differentiation

• germ cells move into cortex
• differentiation into ovary occurs 12 weeks
• oogonia undergo mitosis and then arrest in early
  meiosis as primary oocytes

8
Differentiation of female genitalia, sex
accessory structures

• if testosterone isnt present, genitalia
  feminize
• tubercle clitoris
• urogenital folds labia minora
• labioscrotal swelling labia majora
• Mullerian ducts become oviduct, uterus, cervix,
  vagina
• Wolffian ducts regress

9
Male gonadal differentiation

• occurs weeks 6-7
• requires expression of SRY gene (Sertoli cells?)
• germ cells enter medulla, cortex regresses
• day 60, Leydig cells appear secrete testosterone

10
Differentiation of male sex accessory structures

• testosterone rescues Wolffian ducts
  epididymis, vas deferens, seminal vesicles,
  ejaculatory duct
• Sertoli cells secrete Mullerian inhibiting
  substance (MIS)
• MIS causes regression of Mullerian ducts

11
Differentiation of external genitalia

• Masculinization depends on conversion of
  testosterone to DHT (via enzyme 5 alpha
  reductase)
• if DHT present, genitalia assume male phenotype
  (8th week)
• tubercle penis
• urogenital folds ventral aspect of penis
• labioscrotal swelling scrotum

12
Disorders of sexual development

• INTERSEXUALITY ambiguous reproductive systems
• True hermaphrodites
• combination of gonadal tissues present
• probably due to mosaicism
• sometimes, ovary and Mullerian duct develop on
  one side, testis and Wolffian duct on the other
• Pseudohermaphrodites
• gonads agree with chromosomal sex
• external genitalia resemble that of opposite sex

13
Testicular Feminization Syndrome (MERMs)

• due to insensitivity to androgens (testosterone,
  DHT)
• patients have male chromosomes, normal testes and
  secrete testosterone
• unable to respond to testosterone
• result female external genitalia Wolffian
  ducts dont differentiate
• Mullerian ducts will disappear since Sertoli
  cells still secrete MIS

14
Guevodoces (MERMs)

• eggs at twelve
• common in remote villages of Dominican Republic
• chromosomal males, but female external genitalia
  at birth
• due to deficiency in enzyme 5 alpha reductase
  (converts testosterone to DHT)

15
Guevodoces, contd.

• normal testes present Wolffian ducts
  differentiate
• at puberty, high levels of testosterone override
  deficiency in 5 alpha reductase
• external genitalia is converted to male phenotype
  at puberty
• usually continue life as a male

16
Female Pseudohermaphroditism

• known as ferms
• chromosomal females with ovaries
• external genitalia becomes masculinized
• often due to congenital adrenal hyperplasia
• adrenal glands are unable to make stress hormone
  cortisol secrete androgens instead
• causes masculinization of external genitalia
• can also cause early secondary male sex
  characteristics