Embryology Part 2

Question 1

Summarise the development of limbs

Answer 1

Upper and lower limb buds form (3-4th week)
They develop into protrusions (7th week)
Upper limbs rotate outwards
Lower limbs rotate medially resulting in a helical pattern of lower extremity dermatomes

Question 2

What do you call loss of digits?

Answer 2

Oligodactyly

Question 3

Which stage of pregnancy did thalidomide affect?

Answer 3

First trimester - affected many organs, particularly upper limb development

Question 4

Why is thalidomide still used despite its known complications?

Answer 4

Useful in:
Cancer
Leprosy

Question 5

What is the likely mechanism of action of thalidomide?

Answer 5

Damages developing blood vessels (upper limb blood vessels more sensitive)
Deprives adjacent cells of nutrients and prevents growth

Question 6

Why is the timing of administration particularly pertinent with thalidomide?

Answer 6

Severe morning sickness occurs around 8th week

Limb development also occurs around this time

Question 7

How common is kidney development problems?

Answer 7

Relatively common, and humans can survive with only one kidney

Question 8

What name is given to the immature form of a kidney?

Answer 8

Pronephros

Question 9

What do you call a kidney it its intermediate phase of maturation?

Answer 9

Mesonephros

Question 10

What name is given to the most mature form of a kidney?

Answer 10

Metanephros

Question 11

What is the key thing about pronephros and mesonephros?

Answer 11

They degenerate and DO NOT give rise to the metanephros; this develops independently

Question 12

During which week does the pronephros develop?

Answer 12

Early 4th week

Question 13

Summarise the main stages of human kidney development i.e. when the various stages develop and degenerate

Answer 13

Early 4th week - pronephros development
6th week - degeneration of pronephros and development of mesonephros
8th week - degeneration of mesonephros and differentiation of metanephric tissue

Question 14

Describe the movement of the kidney during development and what aids it.

Answer 14

Metanephros starts off caudally, and moves rostrally via extension of the ureter.

Question 15

What happens to renal arteries as the kidney moves upwards?

Answer 15

New connections with developing arterial system formed as kidneys move, therefore renal arteries break down and re-form

Question 16

State three abnormalities of the kidney that can arise during development

Answer 16

Horseshoe kidney (fusion of distal end of two kidneys)
Retainment of one kidney in pelvis 
Retention of an extra artery e.g. underneath ureter-> obstruction of ureter -> enlargement of renal pelvis

Question 17

What forms within the mesonephros and when are they identifiable?

Answer 17

Mesonephric and paramesonephric ducts; identifiable by 5th week

Question 18

Which duct gives rise to male genital ducts, and what is another name for this?

Answer 18

Mesonephric duct

also known as Wolffian system

Question 19

Which duct gives rise to female genital ducts, and what is another name for this?

Answer 19

Paramesonephric duct

also known as Mullerian system

Question 20

Which layer of the trilaminar disc gives rise to the gonads?

Answer 20

Intermediate mesoderm

Question 21

Which cells cover the gonadal precursor?

Answer 21

Coelomic epithelial cells

Question 22

Which cells give rise to the gametes and where do these originate from?

Answer 22

Primordial germ cells (separate pathway); originate in epiblast

Question 23

Describe the movement of primordial germ cells towards the gonads

Answer 23

Originate from epiblast
Migrate to caudal part of yolk sac
Migrate through the hind-gut and dorsal mesentery to mesonephros
Travel from mesonephros to gonads

Question 24

By which week is the urogenital tract neither male nor female?

Answer 24

By the 7th week

Question 25

What protein and gene influences differential development of the male reproductive system?

Answer 25

SRY (sex-determining region of the Y chromosome)

Question 26

What happens in the absence of SRY and WHEN does this happen?

Answer 26

The female tract, gonads and genital pattern develops; 8-9th week post fertilisation

Question 27

What does SRY cause and what is the time frame?

Answer 27

SRY causes conversion of the indifferent system to the male tract, gonadal pattern and genital pattern Over 3 weeks

Question 28

State the key hormone involved in male development, its origin and what stimulates its production and also the regulatory hormone which influences differentiation of indifferent genitalia into male or female structures?

Answer 28

Dihydrotestosterone - differentiation (also from Leydig cells) Testosterone - from Leydig cells supports development of the Wolffian ducts Testosterone production is stimulated by hCG

Question 29

What is the significance of the timing and stimulation of male development?

Answer 29

Male development starts around weeks 7-8 when hCG is also close to its peak

Question 30

What happens to the paramesonephric ducts during male development? State the hormone involved.

Answer 30

It regresses due to anti-Mullerian hormone (AMH)

Question 31

Which cells produce AMH?

Answer 31

Fetal sertoli cells

Question 32

What else do Leydig cells produce which influences the differentiation of indifferent genitalia into male or female structures?

Answer 32

Dihydrotestosterone

Question 33

What are the most common causes of male mal-development?

Answer 33

Inability to produce the appropriate hormones | Inability of target tissues to respond to these hormones

Question 34

Give an example and explain a receptor defect leading to mal-development of males

Answer 34

Androgen Insensitivity Syndrome - mutant androgen receptor

Question 35

What is another name for androgen insensitivity syndrome?

Answer 35

Testicular Feminisation syndrome

Question 36

Explain the presentation of AIS

Answer 36

External genitalia look female Internally, Wolffian ducts are rudimentary or lacking Testis do not descend

Question 37

Why do people with AIS not develop internal female genitalia e.g. ovaries and uterus?

Answer 37

The sertoli cells remain normal, therefore AMH is still produced and stimulates regression of the paramesonephric duct

Question 38

What are the three types of AIS?

Answer 38

Mild Moderate Complex

Question 39

Name a disorder causing female mal-development

Answer 39

Congenital adrenal hyperplasia

Question 40

What is usually the cause of CAH?

Answer 40

Mutation in Cytochrome P450 21-hydroxylase enzyme (CYP 21A2)

Question 41

Explain the consequence of the 21-hydroxylase deficiency in CAH and how does this relate to the phenotype?

Answer 41

``` Limited cortisol synthesis No negative feedback on ACTH therefore high ACTH Over-stimulation of fetal adrenals Weak androgen production Partial virilisation of genitalia ```

Question 42

What are the internal systems of somebody with CAH?

Answer 42

Still female because there's no SRY, testosterone or AMH due to lack of Sertoli cells