M2-Lecture3

Question 1

In Europe, placental weight is often expressed as a percentage of fetal weight, while North Americans typically use the inverse ratio, with a placenta weighing about 15% of fetal weight indicating a fetus 6.7 times heavier.

Question 2

The placenta can alter its growth trajectory according to the availability of nutrients

Question 3

Adequate fetal growth and development depends on an adequate placenta

The placenta, like other organs, has critical windows of plasticity during development

Failure to mount a robust response to external insults can lead to placental insufficiency and fetal compromise

Question 4

Farmers have long adjusted the nutrition of ewes to produce larger lambs at birth by initially placing well-fed ewes on poor pasture to encourage rapid placental growth and vascular expansion. Once the placenta has developed, the ewes are returned to nutrient-rich pasture, allowing the fetus to grow larger thanks to the enhanced placental support. Similar strategies and outcomes can be observed in human pregnancies, highlighting the importance of maternal nutrition on fetal growth.

Question 5

The placenta plays a crucial role in fetal programming, as disturbances in the maternal environment can disrupt key developmental phases and increase the risk of adult diseases. Changes in placental structure and function in response to these disturbances affect nutrient and oxygen supply, as well as the release of hormones and signaling molecules into the fetal circulation. Consequently, the placenta’s adaptations to reduced blood flow or altered maternal nutrition can significantly influence the fetus’s programming for future health issues.

Question 6

one contributor to FGR: Insufficient remodeling of the spiral arteries  reduction in nutrient and oxygen delivery

even with adequate nutrient availability

Answer 6

Placental dysfunction

Question 6

The placenta’s capacity for nutrient transport can be altered by changes in transporter

Answer 6

Number
Density
Distribution
Activity

Question 7

Nutrient transport across the placenta involves the syncytiotrophoblast (SCTB) and fetal endothelium, facilitating the movement of glucose, amino acids, and fatty acids. Glucose is primarily transported via GLUT1, while small neutral amino acids use System A and L transporters. Maternal triglycerides are converted into free fatty acids (FFAs) by lipoprotein lipase and endothelial lipase, then transported through various proteins (FATPs, FAT/CD36) across the placenta.

Question 8

Another cause of FGR:

Inadequate food supply or deliberate calorie restriction

Answer 8

Maternal undernutrition (insufficient availability of nutrients)

Question 9

GDM and maternal obesity may be the result of:

Answer 9

positive energy balance
Net surplus of hormones (insulin)
Dysregulated growth factors

Question 10

consequence of GDM and maternal obesity:

Answer 10

Fetal overgrowth (Macrosomia)

Question 11

GDM: Maternal hyperglycemia and hyperlipidemia

Maternal Obesity/Excessive GWG: Maternal hyperlipidemia

Answer 11

Frequently larger placentas
Fetal overgrowth
Increased neonatal fat mass/body fat %

Question 12

High maternal fat levels lead to higher accumulation of fat in the fetus. WhY?

Answer 12

The placenta adapts to increased supply of nutrients

Question 13

What is a primary cause of fetal growth restriction (FGR) at high altitudes and is also associated with preeclampsia (PE)

Answer 13

Hypoxia

Question 14

Pregnancies at high altitudes show specific morphological changes in the placenta, list examples:

Answer 14

Such as increased villous vascularization, thinner villous membranes, and greater proliferation of villous cytotrophoblasts as compensatory responses

Question 15

Consequences of these morphological changes at high altitudes:

Answer 15

Reduced expression & activity of placental nutrient transporters

Question 16

What is a major regulator of oxygen homeostasis within cells. As a transcription factor, it affects and regulates the expression of dozens of genes involved in maintaining homeostasis as oxygen concentrations change

Answer 16

HIF-1

Question 17

Maternal conditions like obesity and diabetes can cause placental inflammation, linked to slower growth in preterm infants and long-term health risks. In these cases, traditional inflammation definitions may not apply, as “metaflammation” arises from chronic low-grade inflammation due to excess nutrients. This state can impair placental function and release proinflammatory cytokines into the fetal circulation, affecting fetal programming.

Question 18

Chronic inflammation in the placenta, associated with slower growth in preterm infants and future chronic diseases, challenges traditional inflammation definitions, particularly in obesity and gestational diabetes. This “metaflammation” results from nutrient overload, leading to chronic low-level inflammation without typical immune responses. Stressors like poor nutrition can worsen this, impacting fetal development and causing lasting pro-inflammatory effects into later life.

Question 19

Refers to a low-level, chronic inflammatory state that persists without the typical signs of acute inflammation

Answer 19

Smoldering inflammation

Question 20

refers to a group of infections known to cause congenital anomalies:

Answer 20

TORCH

Oxoplasmosis, Other (including syphilis, varicella-zoster, and parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes.

Question 21

TORCh can lead to complications such as spontaneous abortion, preterm birth, fetal growth restriction (FGR), and a range of birth defects. These infections can infect the placenta and be transmitted vertically to the embryo or fetus.

Answer 21

True

Question 22

primarily transmitted through bites from infected Aedes mosquitoes, which are active both day and night. When a pregnant woman is infected, it can lead to birth defects such as microcephaly and severe fetal brain abnormalities, along with neurodevelopmental issues like hearing and vision problems, limited joint mobility, seizures, excessive muscle tone, swallowing difficulties, and potential developmental delays.

Answer 22

Zika virus

Question 23

A high viral load of Zika virus during pregnancy is associated with more severe effects, including reduced brain size and cognitive issues in the fetus. While the placenta attempts to block some of the virus, Zika can still penetrate through its layers and potentially reach the developing fetus, leading to various complications.

Question 24

Changes in placental structure and function affect nutrient and oxygen supply, as well as the secretion of hormones and signaling molecules into the fetal bloodstream. Consequently, factors like restricted blood flow or altered maternal nutrition can influence fetal programming and future health outcomes.

Question 25

What term refers to effect being not the same between male and female:

Answer 25

Sexual dimorphism

Question 26

Male fetuses are at higher risk for adverse pregnancy outcomes due to sex-specific differences in placental function. Male placentas tend to have more inflammatory gene expression (unable to adapt effectively to maternal stressors unlike female) and faster growth, while female placentas show stronger immune regulation. These differences influence how each sex responds to environmental factors during pregnancy.

Question 27

Males more effort into fetal development while female more effort into placental development. Exposure could harm the male’s placenta and the placenta may not function properly toptorect the fetus. Vs females

Question 28

Males are more significantly impacted than females by adverse conditions, with female placentas showing metabolic adaptations like fatty acid accumulation that help protect the fetus from dyslipidemia.

Question 29

The mechanisms behind sexual dimorphism in placental development and function are not fully understood. They may involve:

Answer 29

Sex Chromosomes: Differential gene expression may result from selective escape of transcripts from X-inactivation.

Epimutations: Variations in sex-specific methylation patterns and gene expression.

Imprinted Genes: Different expression based on sex.

Gonadal Hormones: Hormones that influence placental function.