Development Programming Of Non Mammalian

Question 1

What are predictive adaptive responses?

Answer 1

induced by environmental factors in early life; act via developmental
plasticity to modify the phenotype so that it is matched to the
predicted environment in later life

E.g. in locust: Overcrowding induces offspring to have long wings and
melanised body – Not a “genetic” adaptation

E.g. in alligator: Temperature-dependent sex determination (TSD) with male-promoting t at 33oC during a thermosensitive period of gonadogenesis

E.g. in honeybee: Nurse bees limit the amount of food and its sugar content delivered to larvae, which limits adult body mass and the ovariole number through cell death

E.g. in Sea turtle: TSD, with males produced at 26-27oC and
females at 32-33oC.

E.g. Zebrafish: Remarkable resistance to hypoxia - low cardiac activity and cellular proliferation to minimise O2 consumption

E.g. Japanese quail: Pre-hatching stress and post-hatching unpredictable food availability leads to more risk-taking, explorative behaviour in adulthood – increases the chances of food acquisition in suboptimal environment

E.g. Chicken: Eggs at high altitude decrease their shell porosity to limit water loss (porosity ∝ decreasing Pa)

Question 2

Why do we use non-mammalian species rather than mammalian when studying developmental programming?

Answer 2

Animals have different critical windows of development. Non mammalian often match human critical windows more.

E.g. in chicks:
• Timing of heart development similar to human
• Effects of environment and drug independent of maternal /placental physiology
• Large embryo
• Large numbers in short time
• Cost-effective
• Anatomical difference

E.g in zebrafish:
• Gene map established
• Transparent embryo to monitor blood flow in vivo
• Large numbers in short time
• Single vs. double circulation system
• Regenerative heart – like human fetus

Sheep are expensive and difficult to assess.
Mice are useful but have diff critical windows.

Question 3

Effects of fetal hypoxia?

Answer 3

Caused by placental insuff, abruption, gestational diabetes, maternal obesity, hypertension, high altitide preggo, maternal smoking—>

Leads to vascular constriction in placenta resulting in reduced blood flow and less o2 to fetus—>

Chronic fetal hypoxia and intrauterine growth restriction (IUGR)—>

Developmental programming of cardiovascular and metabolic disease in adulthood.

Question 4

Treatment for reduced blood flow in placenta and fetus by ROS production during preggo?

Answer 4

Antioxidants: Melatonin, Statin, Sildenafil, Vitamin-C, polyphenol, omega 3 etc

Act on the placenta → vasodilation → increase blood flow → more
O2 and nutrient delivery to the fetus → improve fetal development?

Question 5

Effect of antioxidants in study using chick embryos?

Answer 5

• Melatonin, sildenafil, statin, and other antioxidants have no effect on haematocrit, body weight or brain sparing in the chick embryo
• Antioxidants do not make embryos “less hypoxic”
• But…antioxidants improved fetal growth in mammals
• Antioxidants act at the placenta in mammals

Question 6

Effects of hypoxia on cardiac function in chick study? How do antioxidants effect the results?

Answer 6

• Left ventricular developed pressure (LVDP): → How well the heart is contracting
→ Reduced in Hypoxia. Weak heart.
—> Melatonin restored normal LVDP in the hypoxic embryo

• Left ventricular end diastolic pressure (LVEDP): → How well the heart is relaxing
→ Increased in Hypoxia. Impaired relaxability.
—> Statin restored LVEDP in the hypoxic embryo

Antioxidants may have direct effects on the fetus