Introduction to Development and Ageing Flashcards
What are the trends of development and ageing?
More older population so burden of disease increase
Why do you study development?
- understanding birth defects
- understanding cancer
How common are birth defects and what are they caused by?
- 2-5% births have a recognisable birth defect
- 70-75% of unknown cause
- Responsible for up to 70% of neonatal deaths (before 1 month) in 1995
- Responsible for 22% of infant deaths (up to 15 months) in 1995
What is the trend with increasing maternal age and birth defects?
- Age at which families are being started is increasing
- This is at odds with increased sub fertility/birth defects
What are the normal processes of developmental biology?
- proliferation
- apoptosis
- migration
- responsiveness to local signals and neighbouring cells
- unrestrained developmental processes underpin the pathophysiology of cancer
What is the Brenner hypothesis?
- Could variations/disruptions in development underpin common/chronic diseases
- Could nephron number determine risk of hypertension in later life?
- Opportunities of tissue repair?
What is the Barker hypothesis?
- Impact of the uterine environment ‘programmes’ the fetus for postnatal life
- Low birth weight or premature birth associated with risk of cardiovascular disease in adulthood
- Evidence for link to hypertension, T2D and others
What are potential stressors for fetal origins of adult disease?
- Endocrine (cortisol)
- Nutritional
- Extrinsic toxicants (e.g. smoking)
What is epigenetic modification?
- heritable changes to the DNA which do not alter the sequence of bases.
- Stressors are not altering sequence of ACTGs but chemical changes of how DNA interpreted, how genes switched on and off can be altered
What do you chart for child development?
- Gross motor control
- Fine motor control
- Cognitive development
- Language development
- Social and emotional development
Where does fertilisation happen?
-Occurs within the fallopian tube
What does fertilisation trigger?
cortical reaction
What happens in the cortical reaction?
- Cortical granules release molecules which degrade Zona Pellucida (e.g. ZP2 and 3)
- Therefore prevents further sperm binding as no receptors
- Haploid to diploid
What are the stages in the development of conceptus?
- Continues to divide as it moves down Fallopian tube to uterus (3-4 days)
- Receives nutrients from uterine secretions
- This free-living phase can last for ~ 9-10 days
What is the attachment phase in implantation?
outer trophoblast cells contact uterine surface epithelium
What is the decidualisation phase in implantation?
Then
-changes in underlying uterine stromal tissue (within a few hours)
•Requires progesterone domination in the presence of oestrogen
What does leukaemia inhibitory factor (LIF) do in attachment?
Leukaemia inhibitory factor (LIF) from endometrial cells stimulates adhesion of blastocyst to endometrial cells
What does interleukin-11 (IL11) do in attachment?
also from endometrial cells is released into uterine fluid, and may be involved
What other molecules are involved in attachment process?
Many other molecules involved in process (e.g. HB-EGF)
What are the endometrial changes due to progesterone in decidualisation?
- Glandular epithelial secretion
- Glycogen accumulation in stromal cell cytoplasm
- Growth of capillaries
- Increased vascular permeability (→oedema)
What are the factors involved in decidualisation?
- Interleukin-11 (IL11)
- histamine
- certain prostaglandins
- TGFb (TGFb promotes angiogenesis)
