Midterm Flashcards
How does obesity effect pregnancy?
Human pregnancy is an insulin-resistant state with a 40-50% increase in insulin resistance due to the need for increased energy stores. As obesity rates rise, it means the mother is already in a state of increased insulin and inflammation. This causes an increase in early nutrient availability for the fetus which causes increased, early fetal placental growth especially in the adipose tissues late in gestation.
What are some costs of preterm labour?
Admission to hospital can cause anxiety from familial separation and cost, the corticosteroid therapy has long-term effects, and the tocolytic medication can cause maternal and fetal side effects. Most of the time the woman won’t deliver pre-term anyway.
What are the hertfordshire records?
A ledge by Ethel Margaret Burnside that recorded birth, weight at birth and one year, illness, and health. Scientists used this to study later life outcomes. Found that babies born on the low end of normal bw were more likely to die of coronary heart disease. Also found an association with the risk of obesity, type 2 diabetes, and high lipid levels.
What did the dutch hunger winter reveal?
Revealed that famine in utero was detrimental to the long term health of the child. Introduced the idea of critical windows of vulnerability since the time of the exposure greatly affected the health effects.
What did the helsini birth cohort reveal?
Showed that boys and girls who would later get CHD had poor growth from birth to age 2, after which growth steadily increased. Found that thinness at 2 years and high BMI at 11 years is associated with CHD.
What occurs when the appropriate stimulus is applied at the correct window? If not?
In correct, it results in differentiation and maturation, optimal growth (in utero and postnatal), birth at term, and health until old age.
If not correct stimulus or window, can cause preterm birth, IUGR, low birthweight, catch-up growth, and increased adiposity, all resulting in programming and vulnerability to disease.
What are the philosophies of DOHaD?
A baby lives off it’s (grand)mother’s lifetime of experiences
The golden mean (happy medium)
The nature of the child (early life experiences cause disease)
What is DOHaD?
Exposure to altered environments during critical periods of development may alter function of physiological systems in mothers, fathers, and offspring and change postnatal set points.
What is developmental plasticity?
The ability to adapt to our environment and stimuli we are exposed to.
What are the different stages of early development?
- Fertilization: ovulation (ovum moves into tubes), fertilization creating zygote, moves down tube and cell divisions occur.
- Development of blastocyst: cell continue to divide becoming blastocyst and implanting in uterine lining.
- Development of embryo: develops in amniotic sac under uterine lining. Internal organs and body structures form.
- Development of fetus and placenta.
What are some developmental milestones?
Gastrulation: formation of 3 germ layers, gut, notochord by cell migration/division, primitive body plan fixed
Organogenesis: formation of organs/organ systems
Morphogenesis: development/differentiation of structures and form
Cellular differentiation: specialization of cells
Functional maturation: attainment of functional capacity of cell, tissue, organ
What is morphological memory?
In response to adversity, the fetus makes a series of physiological adaptations (that can be permanent) to survive. Can cause a decline in the number of cells and their function, causing disease and early threshold crossing. Adaptations may be mismatched to the long-term post-natal environment.
What are the different functions of the placenta?
Lungs, liver, gut, kidneys, endocrine glands, and defensive barriers. Large surface area and thin membrane separating maternal and fetal circulations allow exchange. Overall, provides oxygen and nutrients, removes waste products, produces hormones, and protects the fetus from endogenous factors.
After the blastocyst hatches from the zone pellucida, what two layers do the TB cells differentiate into?
The inner cytotrophoblast (CTB)
The outer syncytiotrophoblast (STB)
Describe the implantation of the zygote.
- TB lacunae are fluid filled spaces in the tissue.
- Maternal capillaries erode and maternal blood flows into the space in the lacunae.
- Lacunae fuse to form the intravillious space and grow all the way around the conceptus.
- Invasive growth of STB stops at the endometrium implantation site and does not grow into the maternal tissues.
What is decidualisation?
The transformation of the secretory endometrium into the decidua. The endometrial stromal cells change and store glycogen and lipids. Leukocytes from the mother infiltrate.
What are the different layers of the decidua?
Decidua basalis: maternal component of the placenta
Decidua parietalis: decidua lining the rest of the uterine cavity.
Decidua capsularis: superficial layer covering the chorion laeve
Describe the development of the placental villi.
Early on the embryo is fed through diffusion. As it grows, the nutrient demand increases and requires a more robust circulation system.
Primary TB villi: CTB cells penetrate into the buds of the STB
Secondary villi: mesoblasts grow into the primary, and villi expand into the lacunae that are filled with maternal blood.
Tertiary villi: mesoblasts begin to differentiate into specialized cells into connective tissue and blood vessels.
CTB will eventually disappear as the villi wall becomes thin, decreasing the distance between the maternal and fetal blood and allowing free exchange.
What occurs after the final branching of the villi?
The branches that deliver blood to the placenta undergo remodelling. They undergo dilation in order to meet the increasing demands of the fetus. Smooth muscle cells are lost from the walls of the spiral arteries. The EVT proliferate and migrate away from the placenta, down the lumen and through endometrial stroma. They interact with uNK cells to mediate spiral artery remodelling and the colonizing on the walls causes the opening to close.
What are some different methods of exchange at the maternal-fetal interface?
Diffusion: O2, CO2, fats, alcohol
Osmosis: H2O
Simplified transport: glucose via GLUTs (facilitated diffusion and transport)
Active transport: amino acids and peptides to form proteins on fetal side
Vesicular transport: macromolecules via endo/exocytosis in STB cells
What is the main source of energy and nutrition in the fetus?
Glucose. Placental TB cells can synthesize and store glycogen for local glucose requirements. Placental hormones modify the maternal metabolism (insulin resistance) to maximize glucose transfer to fetus.
How does the placenta act as an endocrine organ?
Before pregnancy: hormone production ensured by ovarian and pituitary hormones
Beginning of pregnancy: corpus luteum synthesizes estrogen and progesterone, maintained by human chorionic gonadotropin
During pregnancy: maternal hormones are regulated by placenta, pituitary, and fetal adrenal glands and gonads.
How does the placenta act as lungs?
Oxygenated blood from the placenta enters the RA via inferior vena cava. It by-passes the lung by going through the foramen ovale into the LA. Blood again passes lungs, going up aortic arch and through ductus arteriosus into the aorta. When blood leaves the placenta, the ductus venosus shuttles it away from the liver and towards the heart.
How is immunity transferred to the fetus?
The immune system is complete at the time of birth but the maturation of specific defences is delayed to conserve energy and nutrients. Once born, these developmental delays are countered by the transport of maternal immune factors to the infant by the placenta and breast milk.
How does immunity get transferred?
FcRn receptors localized to STB cells bind to the maternal IGG and shuttle it across the STB layer, releasing it into the CTB. As the CTB layer thins during gestation, more Abs can move across, causing an increase in fetal IgG with advancing gestational age.
How are the placenta and IUGR related?
Placental size accounts for much of the size variation at birth and placental insufficiency is a major cause of IUGR due to limited oxygen and nutrient delivery to the fetus.
What occurs in FGR pregnancies that cause restricted fetal growth?
In FGR or preeclampsia, the depth of the EVT invasion is reduced which means less remodelling by the EVT. This causes blood to flow at a higher pressure and be more pulsatile. This causes increased placental stress, reduced placental development, and overall poor fetal growth.
How can poor nutrition affect the placenta?
Poor nutrition can effect the architecture of the placenta, UN more so than ON. HF placentae may compensate for an excessive nutritional environment by reducing glucose storage. UN placentae may have reduced endocrine function. It can also affect the selective barrier function of the placenta.
How is glucose transported across the placental barrier?
It is transported by GLUT transporters down a concentration gradient. The fetal glucose is therefore determined by the placental consumption and transport. High fetal glucose results in decreased diffusion to fetus and increased placental consumption.
How does GDM effect glucose transporters?
Obesity and the type of GDM treatments have different impacts on pregnancy outcomes, including placental transport function. Non-obese women with insulin controlled-GDM have higher protein and mRNA expression of GLUT1 vs. diet controlled or healthy where as obese women with insulin controlled-GDN have reduced mRNA expression GLUT4 vs. diet control and obese, non-diabetic.
How does GDM affect amino acid transport?
System A (Na dependant of polar or neutral aa) is higher in women with GDM, with or without LGA babies vs. healthy controls. System L (Na indépendant of large neutral, branched, aromatic aa) is higher in women with GDM with LGA babies vs. healthy controls
How does maternal UN affect aa transport?
UN has been shown to reduce expression of aa and GLUT1 transporters in a baboon model, with associated reduction in fetal and placental weights.
What are ABC transporters?
Transporters that are critical for translocation out of the cell, transporting nutrients, steroids, xenobiotics, and various other things. They limit the absorption of stuff into the blood and help form a selective barrier and confer productions at key areas in the body during pregnancy, such as the placenta and the brain.
How does malnutrition effect the placental drug transport system?
Systems become dysregulated due to altered expression of ABC transporters. Women with GDM, regardless of BMI, expression of Abcb1a is lower. Abcb1 is lower in overweight/obese women with GDM. These altered transport mechanisms may result in increased fetal exposure to maternally derived metabolites, toxins, xenobiotics, and hormones. This reduced defensive barrier may also enable inflammatory mediators to enter the fetal compartment.
When is fetal development particularly impaired?
Pregnancies where malnutrition, inflammation/infection, and medication use coexist. Ex. place with high risk of infectious diseases, poor access to clean water, and malnutrition.
What occurs if immune placental programming is altered?
This will adversely effect the immune system of the development of the offspring. This may be caused by maternal malnutrition as the quantity or quality of the immune factors available for transfer are effected. Poor placental development can also cause this and it would reduce transfer of ab to the fetus.
How is Zika associated with the placenta?
Maternal infection with ZIKV during pregnancy can cause IUGR, spontaneous abortions, and microcephaly, resulting in a need to understand how the virus is crossing the placenta. ZIKV infects and replicated in placental macrophages as well as CTB cells, causing minimal cell death but still causing damage while allowing function to be maintained. Timing is important, as ZIKV results in higher viral lodes in the amniotic epithelial cells from mid-gestation to late-gestation placentae.
How is the fetus protected from cortisol and other glucocorticoids?
11BHSD-1 and 1 enzymes that inactivates cortisol to cortisone once in the placenta to prevent high levels of maternal cortisol in the fetus.
Why are glucocorticoids important in pregnancy?
They help mature many organ systems when given at the right time in development. Vital to the timing of normal pregnancies.
How does maternal malnutrition alter the placental GC barrier?
UN: saw a decrease in the amount of GC enzyme at day 50 resulting in a reduced barrier and a higher than healthy exposure level.
Dieting: caused reduced placental GC barrier due to lower levels of enzymes.
What are the different perspectives on brain development?
Structural development: studied and correlated with the mergence of behaviour
Behavioural development: can be analyzed and predictions made about what underlying circuitry must be emerging
Factors that influence both brain structure and behavioural development can be studied
What are the cellular origins of the nervous system?
Blastocyst undergoes gastrulation, rearranging into a multi-layered structure (ectoderm, mesoderm, endoderm)
