Pathophysiology of development

• Abnormalities of sexual development can be caused by

  • Genetic abnormalities
  • Hormonal abnormalities
  • Non specific teratogenic influences
• Non Disjunction


  A pair of chromosomes fail to separate, so that both go to the daughter cells during meiosis
• Types of abnormal zygotes formed by non-disjunction

  • X0
  • XXX
  • YO
  • XXY
• XO


  Gonads are rudimentary or absent so that female external genitalia develop. Stature is short, other congenital anomalies are often present and no maturation occurs at puberty. Called gonadal dysgenesis/ovarian agenesis/turners syndrome.
• XXY


  Most common sex chromosome disorder. Male genitalia. Testosterone secretion at puberty is often enough for the development of male characteristics, however, the seminiferous tubules are abnormal and there is a higher-than-normal incidence of mental retardation. Syndrome is known as seminiferous tubule dysgenesis/Klinefelters syndrome.
• XXX


  Superfemale pattern. Not associated with any characteristic abnormalities.
• YO


  Lethal. Fetus dies in utero.
• Mosaicism


  True hermaphroditism results from faulty mitosis in the early zygote resulting in the production of a mosaic- an individual with both ovaries and testes- an xx/xy mosaicism.
• Pseudo hermaphrodite


  An individual with the genetic constitution and gonads of one sex and the genitalia of the other sex.
• Opposite karyotypes


  • Caused by the transposition of parts of the chromosome to other chromosomes
  • Deletion of the SRY gene on the Y chromosomes produces females with the XY karyotype
• Non disjunction of autosomal chromosomes

  Non disjunction of chromosome 21 produces trisomy 21 associated with Downs syndrome(mongolism)- Case of gene excess. Common in the aged mothers because non disjunction occurs more in the ovary than the testis.
• Chromosomal abnormalities diagnosed by

  • Amniocentesis- sample of amniotic fluid collected by inserting a needle through the abdominal wall and analyzing fetal cell
  • Chorionic villus sampling- Needle biopsy of chorionic villi and examination of fetal cells
• Pseudohermaphroditism


  An individual with the genetic constitution and gonads of one sex and the genitalia of the other sex
• Types of pseudohermaphroditism


  • Female pseudohermaphrodites
  • Male pseudohermaphrodites
• Female pseudohermaphrodites


  Genetic females xx exposed to androgens from some other sources during the 8th-13th weeks of gestation. (Note that exposure after 13 weeks causes hypertrophy of the clitoris)
• Causes of female pseudohermaphroditism

  • Androgens administered to the mother
  • Congenital virilizing adrenal hyperplasia
• Male pseudohermaphrodites


  Development of female external genitalia in genetic males
• Causes of male pseudohermaphroditism

  • Defective embryonic testes- Fail to secrete testosterone and MIS resulting in formation of female genitalia
  • Congenital blockage of the formation of pregnenolone- needed for formation of both testicular as well as adrenal androgens
  • Congenital deficiency of 17 alpha hydroxylase
  • Congenital abnormalities that result in androgen resistance
• Examples of congenital abnormalities that result in androgen resistance

  • 5 alpha reductase deficiency which results in failure of conversion of testosterone to the more active DHT
  • Mutations in androgen receptor genes- Mild results in infertility + or – gynaecomastia. Severe results in testicular feminizing syndrome/complete androgen resistance syndrome
• Testicular feminizing syndrome/complete androgen resistance syndrome


  TFS-MIS is present and testosterone is normal/elevated. External genitalia is female, but the vagina ends blindly-No female internal genitalia.
• Uterus anomalies


  1. Anomalies related to the development of the uterus are caused by abnormal fusion or regression of the caudal paramesonephric ducts. Recall that the caudal segments of the paramesonephric ducts fuse with each other to form the uterus and the upper vagina.

  2. Incomplete fusion of these caudal segments leads to the development of duplicated uterus with or without duplicated vagina.

  3. The uterine septum, being the transient structure that results from the fusion of these caudal segments, normally regresses. Failure of the uterine septum to regress leads to the development of bicornuate uterus (two uterine bodies and one cervix), a septated uterus,or a cervical atresia.

  4. In instances when one paramesonephric duct completely regresses or fails to elongate during embryonic development, this leads to a unicornuate uterus (half a uterus). Although women with paramesonephric duct anomalies can conceive, they have higher rates of spontaneous abortion, premature delivery, and dystocia.
• Male genitalia anomalies


  1. Male genitalia anomalies such as hypospadias and epispadias are caused by incomplete fusion of the urethral folds. This results in an abnormal opening of the penile urethra that occurs along the ventral or inferior aspect of the penis; it could be located near the glans, along the shaft, near the base of the penis, or even along the scrotal raphe. This condition is known as hypospadias.

  2. In instances in which the urethral opening is found on the dorsal or superior aspect of the penis, it is known as epispadias. Although epispadias can occur independently, it is usually associated with exstrophy of the bladder and an abnormal closure of the anterior abdominal wall.
• Cryptorchidism


  1. The failure of a single testis or both testes to descend into the scrotum is known as cryptorchidism. Although many infants may be cryptorchid at birth, the testes may spontaneously descend by three months of age. If the testes have not descended by four to six months of age, they are brought down surgically (orchiopexy).

  2. Individuals with cryptorchidism have a higher risk of developing testicular cancer and can become irreversibly sterile. Testes located in the abdomen are usually three to five degrees warmer than if they were in the scrotum. This can reduce the number of adult type A spermatogonia available for spermatogenesis while increasing the likelihood of promoting germ cells into carcinoma cells.
• Inguinal hernia and hydrocele

  1. Recall that the connection between the abdominal cavity and the processus vaginalis in the scrotum normally becomes obliterated. If it remains open, intestines may descend into the scrotum and cause congenital indirect inguinal hernia.

  2. In instances when the obliteration is incomplete, small fluid-secreting cysts may persist between the parietal and visceral layers of the tunica vaginalis, forming hydrocele of the testis and/or spermatic cord.