Embryology

Question 1

What do urinary and internal reproductive organs develop from?

Answer 1

Both the urinary and internal reproductive organs develop primarily from intermediate mesoderm.

Question 2

Indifferent stage –> male

Answer 2

II. Male and female genital systems are initially similar (indifferent stage). The Y chromosome contains the SRY gene (sex-determining region on Y). The protein product of this gene (Testis-Determining Factor; TDF) masculinizes the indifferent genital system

Question 3

Testes: Indifferent stage

Answer 3

1. Genital (gonadal) ridges form from intermediate mesoderm and overlying epithelium.
2. Epithelium (cortex) grows into underlying mesoderm to form primitive sex cords (medulla).
3. Primordial germ cells (PGC’s)
   a. Migrate to genital ridges week 4-6 PGCs.
   b. If PGC’s do not migrate into the genital ridges, the gonads will not form.

Question 4

Testes: from indifferent gonad to testes

Answer 4

B. TDF induces the indifferent gonad to form the testes

1. Medulla of primitive gonad will form testes
   a. The primitive sex cords remain as solid tubes until puberty when they canalize. Then form the seminiferous tubules, tubuli recti, rete testes (intratesticular ducts).
   b. The testes begin to secrete testosterone by week 8.
2. Cortex of primitive gonad will mostly form tunica albuginea

Question 5

Descent of the testes

Answer 5

1. About 97% of newborns are born with descended testes; of those that remain undescended, most will descend within about 3 days after birth.
2. Controlled by testosterone; but exact mechanism remains unknown.
3. Gubernaculum – thick ligament that attaches the caudal pole of the testes to the anterior body wall (future site of deep inguinal ring).
4. Processus vaginalis – an evagination of periotoneum that passes through the abdominal wall lateral to the site of attachment of the gubernaculum.
5. The processus vaginalis and gubernaculum (and thus testes and ductus deferens) are pulled through the abdominal wall, forming the inguinal canal.
6. The proximal portion of the processus vaginalis closes; the distal portion forms tunica vaginalis around testes.

Question 6

Male genital ducts (internal genitalia)

Answer 6

A. Indifferent stage

  1. Two duct systems form from intermediate mesoderm.
  2. Mesonephric (Wolffian) ducts (mostly contribute to male ducts)
  3. Paramesonephric (Mullerian) ducts (mostly contribute to female ducts)

B. Testosterone (from Leydig cells) will induce the mesonephric ducts to differentiate into male genital ducts and glands.

C. Antimüllerian hormone (AMH; produced by Sertoli cells) will inhibit the paramesonephric ducts from developing into female genital ducts.

Question 7

Male genital ducts: Embryonic structures –> male adult derivative

Answer 7

1. Mesonephric tubules – efferent ductules, appendix of the epididymis
2. Mesonephric ducts – epididymis, ductus deferens, ejaculatory duct; seminal vesicle
3. Urethra will give rise to prostate and bulbourethral glands.
4. Paramesonephric duct – regresses, except for: appendix of the testes, prostatic utricle

Question 8

Male external genitalia: development

Answer 8

A. Indifferent stage

1. Cloacal folds – mesenchymal swellings around cloacal membrane
   a. Later divide into urethral and anal folds
   b. Anteriorly the cloacal folds fuse to form the genital tubercle
2. Genital (labioscrotal) swellings form on each side of the cloacal membranes.

B. The external genitalia are not fully differentiated until the 12th week; under influence of testosterone and dihydrotestosterone (a testosterone metabolite).

Question 9

Male external genitalia: embryonic structure –> adult derivative

Answer 9

1. Anal folds – anal canal
   
   2. Genital tubercle – elongates to form the glans penis
   3. Urethral folds – shaft, root of penis and penile urethra
      a. Elongates along with the genital tubercle.
      b. Urethra groove is an open groove on ventral penis.
      c. Later, the two folds fuse to form the penile urethra.
      d. The remaining portion of the urethra (in the glans penis) is formed by ectodermal cells that grow inward.
   4. Labioscrotal swellings – scrotum; scrotal septum forms where the two swellings fuse.

Question 10

Hypospadias

Answer 10

1. Caused by incomplete fusion of the urethral groove on ventral surface of penis.
2. Abnormal opening of penile urethra on ventral surface of penis.
3. Testosterone dependent process.

Question 11

Epispadias

Answer 11

1. Urethral opening is on dorsum of penis.
2. Often occurs with exstrophy of the bladder.
3. Thought to be due to urethral plate developing more dorsally than normal.
4. Testosterone independent.

Question 12

Congenital indirect inguinal hernia

Answer 12

1. Cause: Proximal processus vaginalis remains patent.
2. Intestinal loops pass through open passageway.
3. More common in males

Question 13

Hydrocele

Answer 13

1. Fluid filled sac around scrotum or spermatic cord caused by excessive serous fluid production.
2. Noncommunicating and communicating types.

Question 14

Cryptorchidism

Answer 14

1. Failure of testes to descend into scrotum.
2. Testosterone dependent.
3. Undescended testes will be infertile due to temperature dysregulation.

Question 15

Female development from indifferent stage…

Answer 15

The male and female genital systems are initially similar (indifferent stage). In the absence of SRY (sex-determining region on Y) the female body plan will form. (**other proteins are likely involved).

Question 16

Ovaries: Indifferent stage

Answer 16

1. Genital (gonadal) ridges form from intermediate mesoderm and overlying epithelium.
2. The epithelium grows into underlying mesoderm to form primitive sex cords.
3. Outer cortex; inner medulla.
4. Primordial germ cells (PGC’s) migrate into gonad.

Question 17

Absence of TDF and the ovaries…

Answer 17

B. Absence of TDF induces the indifferent gonad to form the ovary (unknown gene products from the two X chromosomes are also required).

1. The sex cords in the medulla degenerate.
2. A second generation of cortical sex cords form from the epithelium; these will form the follicular cells around the oogonia.
3. Cortex forms ovary; medulla regresses

Question 18

Descent of the ovaries

Answer 18

1. Gubernaculum – will form the ovarian ligament and round ligament of the uterus.
2. Processus vaginalis – very small, obliterates before birth.

Question 19

female genital ducts

Answer 19

A. Indifferent stage

1. Mesonephric ducts (mostly contributes to male ducts)
2. Paramesonephric ducts (mostly contributes to female ducts)
   a. Cranial ends open into abdominal cavity
   b. Caudal ends fuse and enter cloaca.

B. Absence of AMH allows paramesonephric ducts to differentiate into female genital ducts; mesonephric ducts degenerate in the absence of testosterone.

Question 20

Female genital ducts: embryonic structure –> adult derivative

Answer 20

1. Cranial end of paramesonephric ducts – uterine tube
2. Caudal, fused portion of paramesonephric ducts – uterus, cervix, superior vagina.
3. Sinovaginal bulb (vaginal plate) – inferior portion of vagina
   a. Forms from cloaca (urogenital portion); induced by paramesonephric ducts.
   b. Initially, forms a solid tube called the vaginal plate; canalizes by 5th month.
   c. Hymen; thin membrane separating urogenital sinus from vagina.
   d. Urethral endoderm will give rise to greater vestibular and skene’s glands.

Question 21

Female external genitalia: indifferent stage and differentiation

Answer 21

A. Indifferent stage

  1. Cloacal folds – mesenchymal swellings around cloacal membrane
        a. Later divide into urethral and anal folds
         b. Anteriorly the cloacal folds fuse to form the genital tubercle 2. Labioscrotal (genital) swellings form on each side of the cloacal membranes

Question 22

female external genitalia: embryonic structure–> adult derivative

Answer 22

1. Anal folds – anal canal
2. Genital tubercle – elongates to form the clitoris
3. Urethral folds – labia minora
   a. Erectile tissue (bulbs of vestibule; crus of clitoris)
   b. The urethral groove remains unfused and will form the vestibule
4. Labioscrotal swellings – labia majora

Question 23

Uterine and vaginal defects (general)

Answer 23

Most of these defects result from an incomplete fusion of the two paramesonephric ducts.

Question 24

uterus arcuatus

Answer 24

very slight lack of fusion of paramesonephric ducts.

Question 25

uterus bicornis (bicollis)

Answer 25

partial lack of fusion of paramesonephric ducts.

Question 26

Double uterus with double vagina (uterus didelphys

Answer 26

complete lack of fusion of paramesonephric ducts and formation of two sinovaginal bulbs.

Question 27

Uterus bicornis unicollis

Answer 27

caudal portion of 1 paramesonephric duct fails to form.

Question 28

Uterus unicornis

Answer 28

complete agenesis of one paramesonephric duct

Question 29

Vaginal and cervical atresia

Answer 29

atresia of the sinovaginal bulbs or from a failure of canalization.

Question 30

Klinefelter syndrome

Answer 30

1. 47, XXY; male
2. Cause: Nondisjunction during meiosis
3. Infertile due to low levels of testosterone; aspermatogenesis
4. Impaired sexual maturation
5. Gynecomastia

Question 31

Turner syndrome

Answer 31

1. 45, XO
2. Cause: Nondisjunction during meiosis
3. Gonadal dysgenesis; streak gonads
4. External and internal genitalia form normal female (except for ovary)
5. Lack of secondary sex trait development at puberty
6. Short-stature, broad chest, short neck; lymphedema of hands and feet

Question 32

Swyer syndrome

Answer 32

1. 46, XY
2. Cause: Point mutation of SRY gene resulting in defective TDF protein.
3. Gonadal dysgenesis; streak gonads develop.
4. External and internal genitalia form normal female (except for ovaries)
5. Amenorrhea
6. Lack of secondary sex trait development at puberty

Question 33

True hermaphroditism

Answer 33

1. Presence of male and female gonadal tissue (within same or opposite gonad).
2. Ovotestes – ovarian and testis tissue found in same gonad.
3. Most have the 46, XX genotype.
4. Cause is most likely a translocation of portion of Y (containing SRY gene) onto X chromosome during meiosis.
5. Ambiguous external genitalia.
6. Very, very rare!

Question 34

Female pseudohermaphroditism

Answer 34

1. 46, XX
2. Cause: congenital adrenal hyperplasia (excessive production of androgens by adrenal glands).
3. Ovaries develop due to normal functioning of two X chromosomes
4. Internal genitalia form normal female
5. However, timing of excessive production of androgens by the adrenal gland is such that the external genitalia become exposed to high levels of testosterone; results in masculinization of external genitalia

Question 35

Male pseudohermaphroditism

Answer 35

1. 46, XY
2. Testes form (due to normal functioning Y chromosome).
3. CAUSE: Insufficient androgen and AMH production (hypogonadism)
4. External and internal genitalia develop as female

Question 36

Androgen insensitivity syndrome

Answer 36

1. 46, XY
2. Testes develop normally (due to normal functioning Y chromosome)
3. AMH and testosterone production are normal
4. CAUSE: Lack of androgen receptor expression in embryonic tissues
5. Mesonephric ducts degenerate (due to insensitivity to testosterone)
6. Paramesonephric ducts degenerate (due to presence of AMH)
7. No internal reproductive viscera
8. Female external genitalia develop due to testosterone insensitivity (vagina is short and blind-ending)