Embryology Part 2 Flashcards
Summarise the development of limbs
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
What do you call loss of digits?
Oligodactyly
Which stage of pregnancy did thalidomide affect?
First trimester - affected many organs, particularly upper limb development
Why is thalidomide still used despite its known complications?
Useful in:
Cancer
Leprosy
What is the likely mechanism of action of thalidomide?
Damages developing blood vessels (upper limb blood vessels more sensitive)
Deprives adjacent cells of nutrients and prevents growth
Why is the timing of administration particularly pertinent with thalidomide?
Severe morning sickness occurs around 8th week
Limb development also occurs around this time
How common is kidney development problems?
Relatively common, and humans can survive with only one kidney
What name is given to the immature form of a kidney?
Pronephros
What do you call a kidney it its intermediate phase of maturation?
Mesonephros
What name is given to the most mature form of a kidney?
Metanephros
What is the key thing about pronephros and mesonephros?
They degenerate and DO NOT give rise to the metanephros; this develops independently
During which week does the pronephros develop?
Early 4th week
Summarise the main stages of human kidney development i.e. when the various stages develop and degenerate
Early 4th week - pronephros development
6th week - degeneration of pronephros and development of mesonephros
8th week - degeneration of mesonephros and differentiation of metanephric tissue
Describe the movement of the kidney during development and what aids it.
Metanephros starts off caudally, and moves rostrally via extension of the ureter.
What happens to renal arteries as the kidney moves upwards?
New connections with developing arterial system formed as kidneys move, therefore renal arteries break down and re-form
State three abnormalities of the kidney that can arise during development
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
What forms within the mesonephros and when are they identifiable?
Mesonephric and paramesonephric ducts; identifiable by 5th week
Which duct gives rise to male genital ducts, and what is another name for this?
Mesonephric duct
also known as Wolffian system
Which duct gives rise to female genital ducts, and what is another name for this?
Paramesonephric duct
also known as Mullerian system
Which layer of the trilaminar disc gives rise to the gonads?
Intermediate mesoderm
Which cells cover the gonadal precursor?
Coelomic epithelial cells
Which cells give rise to the gametes and where do these originate from?
Primordial germ cells (separate pathway); originate in epiblast
Describe the movement of primordial germ cells towards the gonads
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
By which week is the urogenital tract neither male nor female?
By the 7th week
What protein and gene influences differential development of the male reproductive system?
SRY (sex-determining region of the Y chromosome)
What happens in the absence of SRY and WHEN does this happen?
The female tract, gonads and genital pattern develops; 8-9th week post fertilisation
What does SRY cause and what is the time frame?
SRY causes conversion of the indifferent system to the male tract, gonadal pattern and genital pattern
Over 3 weeks
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?
Dihydrotestosterone - differentiation (also from Leydig cells)
Testosterone - from Leydig cells supports development of the Wolffian ducts
Testosterone production is stimulated by hCG
What is the significance of the timing and stimulation of male development?
Male development starts around weeks 7-8 when hCG is also close to its peak
What happens to the paramesonephric ducts during male development? State the hormone involved.
It regresses due to anti-Mullerian hormone (AMH)
Which cells produce AMH?
Fetal sertoli cells
What else do Leydig cells produce which influences the differentiation of indifferent genitalia into male or female structures?
Dihydrotestosterone
What are the most common causes of male mal-development?
Inability to produce the appropriate hormones
Inability of target tissues to respond to these hormones
Give an example and explain a receptor defect leading to mal-development of males
Androgen Insensitivity Syndrome - mutant androgen receptor
What is another name for androgen insensitivity syndrome?
Testicular Feminisation syndrome
Explain the presentation of AIS
External genitalia look female
Internally, Wolffian ducts are rudimentary or lacking
Testis do not descend
Why do people with AIS not develop internal female genitalia e.g. ovaries and uterus?
The sertoli cells remain normal, therefore AMH is still produced and stimulates regression of the paramesonephric duct
What are the three types of AIS?
Mild
Moderate
Complex
Name a disorder causing female mal-development
Congenital adrenal hyperplasia
What is usually the cause of CAH?
Mutation in Cytochrome P450 21-hydroxylase enzyme (CYP 21A2)
Explain the consequence of the 21-hydroxylase deficiency in CAH and how does this relate to the phenotype?
Limited cortisol synthesis No negative feedback on ACTH therefore high ACTH Over-stimulation of fetal adrenals Weak androgen production Partial virilisation of genitalia
What are the internal systems of somebody with CAH?
Still female because there’s no SRY, testosterone or AMH due to lack of Sertoli cells
