M2-Lecture2 Flashcards
Placenta Development
Vital organ of pregnancy, needed for fetal survival & growth:
Placenta
Placenta is formed from both maternal and embryonic tissue:
True
The placenta functions as lungs, liver, kidney, gut, endocrine glands, & defensive barrier. T/F
True
Functions of the placenta:
Provides oxygen & nutrients to fetus
Removes waste products
Produce hormones
Protects fetus from endogenous factors like infectious substances & maternal immune cells,
maternal hormones,
Xenobotics (foreign substances)
The placent a has to be the right size in diameter, width, thickness. why?
If too small, not enough nutrients pass through, and if too big too many nutrients.
How is primary villous stage formed: Mesoderm connection growing embryo & chorionic plate - connecting stalk
Cytotrophoblast cells proliferate & penetrate into the syncytiotrophoblast
How is secondary villous stage formed:
Mesodermal cells penetrate core of primary villus and grow toward decidua.
How is teritiary villous stage formed:
Core mesodermal cells differentiate into blood cells& small blood vessels.
Term to refer to villi on the embryonic pole continue to grow & expand
Chorion frondosum
Term to refer to vlli on the abembryonic pole degenerate
Chorion laeve
Cytotrophoblast cells in the trophoblastic shell have degenerated except for the
Extravillous cytotrophoblast cells which anchor villi
Extravillous cytotrophoblast cells role:
Remodeling of uterine spiral arteries
Angioblasts (endothelial layer of blood vessels) arise from what:
Purely mesodermal popualtion
What divides placenta into functional units and name of this:
Decidual septa
into
Cotelydons
Individual angioblasts coalesce to form the primary vascular plexus through a process:
vasculogenesis
signals from the adjacent endoderm are necessary to induce angioblast specification within the mesoderm. T/F
True
he angioblasts proliferate and coalesce into cords that then form continuous strands of endothelial cells. These cells then form tubular vascular structures. T/F
True
primary network of blood vessels (aggregation of angioblasts) in the embryo is formed by the process of:
vasculogenesis
Spread of vascular network occurs via angiogenesis. T/F
True
Is critically important for both placental vasculogenesis and angiogenesis throughout gestation:
VEGF
Important for the formation of angioblasts along with the formation of the first mesenchymal villi:
FGF 2 and VEGF
Are critically important for the formation of placental capillary network via sprouting and elongation with the development of the villous tree:
VEGF and PlGF
are upregulated to facilitate the expansion of placental vascular network during the third trimester:
Angiopoietins and many other growth factors
What is the transformation (functional & morphological) of secretory endometrium (decidua):
Decidualization
What happens during decidualization:
Endometrial stromal cells change
- MET
- Store glycogen & lipids
Leukocyte from mother infiltrate
On to which blastocyst impants
Utero-Placental Circulation steps:
Spiral arteries pierce decidual plate and enter the intervillous spaces (IVS)
Blood leaves the intervillous space through endometrial veins
What is the benefit of trophoblast modified artery vs unmodified artery:
Increased flow and reduced resistance
How does this remodelling of uterine spiral arterioles take place:
By extravillous cytotrophoblast cells
What two artery are responsible for blood supply to uterus:
Arcuate and spiral artery
What does the myometrium refer to:
Middle layer of the uterine wall, uterine muscle
Placenta previa occurs when:
Placenta is abnormally placed, totally covers or is in close proximity to internal OS.
Low lying
Marginal
Complete
Placenta previa is common in early pregnancies, but may resolve over course of pregnancy: T/F
True
Signs and symptoms of Placenta previa:
Sudden, painless vaginal bleeding
- Near end of the second trimester or beginning of the third trimester
Visualization on ultrasound
Etiology of Placenta Previa:
Abnormally developed uterus
Multiple pregnancy
Scarring of the uterine wall caused by previous pregnancies, caesareans, uterine surgery, or abortions
Large placenta
Treatment for Placenta previa;
Presentation at term - requires C-section
Abnormally deep attachment of placenta:
Placenta Accreta
Characteristics of placental accreta:
Abnormal attachment to myometrium, partial or complete loss of decidua basails
When placenta penetrates enitre myometrium to uterine serosa:
Placenta percreta
When placenta penetrates into myometrium:
Placenta increta
Risks associated with placenta accreta:
Greater risk of hemorrhage
Hysterectomy (can no longer bear a child)
Etiology/causes of placenta accreta:
Unknown
Previous C-section
Placenta previa
Signs & symptoms of placenta accreta:
Very rarely recognized before birth
Abnormal doppler ultrasound
Severe hemorrhage during delivery
Failure to deliver placenta within 30 min
Placenta accreta treatment:
C-section
Surgery to stem bleeding, removal of damaged tissue
Hysterectomy
Transfer of maternal-fetal exchange dependent upon:
Blood flow
Surface area
Placental metabolism
Passage of substances is bi-directional (follows concentration gradient) for maternal-fetal exchange. T/F
True
Transfer mechanisms in maternal-fetal exchange:
Diffusion
Facilitated diffusion
Osmosis (water)
Active transport
Vesicular transport
What kind of molecules pass through simple diffusion:
Non-polar molecules & fat-soluble substances, including O2, CO2, fats, alcohol
Diffusion follows concentration gradient (high-to-low) until homeostasis is achieved. T/F
True
Simple diffusion is not energy dependent. T/F
True
Diffusion mechanisms that is supported by transport molecules like proteins like carrier proteins/transmembrane proteins, either nonspecific or specific transporter
Facilitated diffusion
Example of facilitated diffusion:
Glucose carrier proteins (GLUTs)
Facilitated diffusion is not energy dependent: T/F
True
Mechanism which allows soluble substances to pass through selectively permeable membrane:
Osmosis
H2O cannot pass through double lipid layer of cellular membrane, but must pass placenta by aquaporines via osmolar gradient:
Yes
H2O exchange increases during pregnancy:
Right
Transport through the cellular membrane against concentration gradient
Requires energy and examples
Active transport (low to high)
ex: amino acids (this transport is influenced by hormones)
List the hormones that influence the active transport of amino acids across the placenta:
GH, TSH (higher in fetus), Leptin
Endocytosis, exocytosis; active in the STB cells
True
Macromolecules, including immunoglobins are captured by microvilli of the STB cells and absorbed into the cell, or excreted from it
he neonatal Fc receptor (FcRn) facilitates the passive transfer of immunoglobulin G (IgG) antibodies from mother to fetus by binding to the Fc portion of IgG, ensuring the transfer of maternal humoral immunity
True
Anti-TNF monoclonal antibodies like infliximab, adalimumab, and golimumab, which have an Fc portion, can be transferred across the placenta, but not those with minimal Fc receptor like Certolizumab
True
Placental functions:
GI
Endocrine organ
Lungs
Barrier
Kidneys
Nutrient transport dependent on
placental size
morphology (exchange zone surface area and tissue thickness)
nutrient transporter capacity/availability
utero- and feto-placental blood flow
What is major determinant of intrauterine growth:
Placental nutrient supply
Nutrition to fetus is by way of criculatory system (parenteral nutrition) rather than fetal digestive tract:
Yes
These are the essential macronutrients for adequate fetal growth, and each nutrient crosses the syncytium through specific transporters
Glucose, amino acids, free fatty acids (FFAs) and cholesterol
The primary form of fat in the body:
Triglyceride (three fatty acids attached to glycerol backbone.
When the body requires energy, triglycerides are broken down through a process called
Go through beta-oxidation to produce acetyl-CoA and then Krebs Cycle
Lipolysis
This occurs mainly in the liver and adipose tissue, where excess glucose is transformed into triglycerides for storage.
Lipogenesis
Glucose is primarily transported via GLUT1, while small neutral amino acids are taken up by System A transporters at both membranes, and fatty acids are hydrolyzed by lipoprotein lipase (LPL) and endothelial lipase (EL) before being transported through fatty acid transport proteins (FATPs) and binding proteins (FABPs).
Yes
Primary energy substrate required for fetal and placental growth
Glucose
Minimal fetal gluconeogenesis
Placental STB cells can synthesise and store glycogen for local glucose requirements (glycogenolysis)
Placental hormones modify maternal metabolism to maximize glucose transfer to fetus.
Yes
Glycerol can be converted to glucose through gluconeogenesis (lactate, amino acids, glycerol):
Go through beta-oxidation to produce acetyl-CoA and then Krebs Cycle
Yes
high-fat diets can produce metabolites that are not beneficial for the fetus
Amino acids play a critical role in the development of fetal tissue
True
Active transport plasma [most amino acids] are ↑ in fetal circulation (so that fetus gets enough amino acids)
True
Fatty acid roles in fetal growth:
Brain development & fat accretion
Fetus can generate some fatty acids (glucose), essential fatty acids (EFAs) come from placental transfer
True
What breaks down maternal TG to FFA and the diffusion type:
TG Lipase
Passive diffusion & facilitated diffusion
The presence of fatty acid transport proteins (FATPs) and fatty acid binding proteins (FABPs) facilitates the efficient uptake and transport of free fatty acids (FFAs) from maternal circulation to the fetus.
Yes
Before pregnancy, ovarian and pituitary hormones prepare the body for conception. At the beginning of pregnancy, the corpus luteum produces estrogen and progesterone, sustained by human chorionic gonadotropin (hCG). During pregnancy, the placenta, along with the pituitary and fetal adrenal glands, regulates maternal hormone levels to support fetal development and maintain the pregnancy.
Yes
Initially secreted by corpus luteum; by ~4th month, placental P4 production is high enough to maintain the pregnancy
Keeps myometrium quiescent during pregnancy (relaxed & prevent premature contractions)
Appetite stimulant
Prevents mammary gland from being activated by prolactin before birth
True
Estradiol (E2) is the primary estrogen during pregnancy, while estriol (E3) is predominantly produced by the placenta, with its synthesis regulated by the fetal adrenal gland from DHEA.
Estriol is crucial for the proliferation of endometrial cells and plays a significant role in the development of mammary glands and milk production after childbirth.
An increase in the ratio of estrogen to progesterone enhances the synthesis of uterine prostaglandins (PGs)
True
Prostaglandins (PGs), which facilitates cervical ripening, increases the elasticity of connective tissue, and promotes uterine contractions, preparing the body for labor.
Prostaglandin
What is synthesized by cytotrophoblast (CTB) and syncytiotrophoblast (STB) cells, plays a crucial role in promoting fetal growth by inducing lipolysis, which increases circulating free fatty acids (FFAs)
It also promotes maternal insulin resistance, inhibits gluconeogenesis, and stimulates maternal beta cell proliferation early in pregnancy, leading to increased insulin levels and fat deposition (to conserve glucose for the fetus). Additionally, it promotes protein synthesis, acts as an appetite stimulant to increase maternal food intake by the end of the first trimester, and supports milk production after childbirth.
Placental lactogen
Placental growth hormone, secreted by syncytiotrophoblast (STB) cells, promotes fetal growth by stimulating gluconeogenesis, lipolysis, and maternal anabolism while regulating insulin-like growth factor (IGF-I) levels. It suppresses maternal pituitary growth hormone secretion and may contribute to maternal insulin resistance (making it hard for her body to use insulin to provide glucose to the fetus).
Leptin, which normally helps control appetite and energy balance, (targets neurons in the hypothalamus) rises during pregnancy due to the placenta and fat stores. However, the mother becomes resistant to leptin, meaning the usual mechanisms that regulate her energy intake and expenditure are disrupted, leading to increased food consumption and fat storage.
Leptin regulates fetal growth by affecting nutrient transport in the placenta, promoting blood vessel formation, and supporting blood cell development. High levels of leptin in cord blood are associated with increased fetal fat, and levels are often elevated in pregnancies with gestational diabetes and preeclampsia.
When a fetus is born prematurely, its lungs are often underdeveloped, which can complicate breathing. Providing pure oxygen can be toxic, so it’s typically mixed with normal air. To aid lung development, the baby may receive cortisol, which supports the maturation of fetal organs, including the lungs, which are filled with fluid until birth.
Placenta is equivalent of the lungs, but 15X less efficient
Shunts
Ductus venosus (by-pass liver)
Formamen ovale (by-pass lung)
Ductus arteriosus (by-pass lung)
These shunts in the fetal circulatory system allow blood to bypass certain organs that are not yet fully functional:
As a barrier, placenta although protects fetus from harmful susbstances, is selective or incomplete against certain compounds:
Permits transfer of immunity to fetus
True
Vaccinating the mother against whooping cough during pregnancy provides antibodies to the newborn, offering temporary immunity until the baby can be vaccinated a few months after birth.
True
cortisol is the primary biologically active glucocorticoid (GC)
Essential to regulate fetal exposure to GC across pregnancy for appropriate fetal development
GC Barrier – the placenta protects fetal organs from elevated cortisol in the maternal circulation
11βHSD-2 converts biologically active cortisol into inactive cortisone
Cortisol levels in the fetal circulation are kept ~ 10-fold lower than the maternal circulation
Birth at term and preterm is characterized by activation
of the fetal hypothalamic-pituitary-adrenal (HPA) axis
and an increase in circulating fetal glucocorticoid (GC)
concentrations
The normal development of the hypothalamic–pituitary–adrenal (HPA) axis is crucial for maintaining intrauterine homeostasis and ensuring the proper differentiation and maturation of essential organ systems, such as the lungs, liver, and central nervous system, which are vital for the newborn’s immediate survival after birth.
Inactive form of cortisol:
Cortisone
The fetus can be infected through the lower genital tract or maternal blood, potentially colonizing the placenta. An intact syncytium protects against these infections, but damage to the placenta weakens this barrier, allowing some pathogens to cause congenital infections, known as TORCH infections.
L. monocytogenes faces multiple barriers when attempting to infect the placenta, starting with extravillous cytotrophoblasts (EVT) as the primary entry point, where phagocytes can transport the bacteria but encounter delays in the EVT’s intracellular life cycle. Additionally, the syncytiotrophoblast (SYN) is highly resistant to infection, and any damage to it may create temporary access points, which are quickly covered by fibrinoid clots, adding another layer of protection against infection.
older strains of COVID-19 have been associated with neurodevelopmental inflammatory responses.
Typical small molecule compounds (Xenobiotics) can cross this barrier through various mechanisms such as passive diffusion, facilitated diffusion, active transport, and cellular processes like phagocytosis or pinocytosis.
The placental barrier limits substance transfer based on size, lipophilicity, and transporter affinity. ABC transporters like MDR1/P-glycoprotein actively pump drugs and xenobiotics back to the maternal circulation, while the placenta also utilizes the cytochrome P450 system for biotransformation, modifying xenobiotics to protect the fetus.
The newborn’s immune system is immature at birth, focusing energy on organ development, but maternal antibodies are transferred through the placenta and breast milk to offer protection.
The FcRn receptor in the syncytiotrophoblast (STB) transports maternal IgG to the cytotrophoblast (CTB), with decreasing CTB thickness during gestation allowing more antibodies to cross and increasing fetal IgG levels.
Placental exchange also involves excretory functions
Placental exchange processes exist to remove waste products of fetal metabolism into maternal blood to be excreted by the mother
E.g. urea, creatinine
