Lecture 8 - Placenta and Fetal Membranes Flashcards
What is the first embryo stage where there are 2 different cells types? What are they?
Blastocyst: intracellular mass (ICM) and trophectoderm
What happens to the trophoblast cells once they reach the uterine stroma?
They differentiate into syncytiotrophoblast (=syncytial trophoblast) and cytotrophoblast (=cellular trophoblast)
What types of cells make up the embryonic portion of the placenta?
- Syncytiotrophoblast
2. Cytotrophoblast
What do the syncitiotrophoblast cells form upon implantation? How? Where is it?
It surrounds the embryo entirely and forms trophoblastic lacuna (fluid filled cavities)
What happens to the trophoblastic lacunae at days 8-12?
Syncytiotrophoblast produces digestive enzymes that eat away at arteriole and veniole capillaries which fills up the lacunae with maternal blood
What tissue lines the chorionic cavity and connects the embryo with yolk sac and amniotic cavity to the endometrium?
Extraembryonic mesoderm
List the 6 layers of the placenta at day 14-15. What is the whole structure with all 6 layers called?
- Extraembryonic mesodern
- Cytotrophoblast
- Syncytiotrophoblast
- Trophoblastic lacuna
- Maternal blood vessels
- Uterine tissues = endometrium
=> primary stem villus
How does the syncytiotrophoblast form?
Once the trophoblast cells enter the stroma they proliferate and loose their membrane resulting in a confluent cytoplasm with many nuclei scattered throughout: the syncytiotrophoblast
How does the primary stem villus develop into a secondary stem villus? Timing?
Signals between the extraembryonic mesoderm and the cytotrophoblast causes the extraembryonic mesoderm cells to proliferate on top of each other and grow into the primary stem villus toward the uterine tissue
Day 14-15
How does the secondary stem villus develop into a tertiary stem villus? Timing?
Cytotrophoblast penetrates through the syncytiotrophoblast to reach the uterine tissue (no cells are broken through though) and the extraembryonic mesoderm that comes along contains chorionic arteries and veins
Day 21
Are the chorionic arteries and veins embryonic?
YUP
How are chorionic arteries and veins formed?
Vasculogenesis of the extraembryonic mesoderm
What is the hemochorial circulation? When does this happen?
Circulation in the placenta when maternal blood is in direct contact with the chorion BUT THE BLOODS DO NOT MIX
At the tertiary stem villus stage (>21 days)
Result on maternal circulation of the development of tertiary stem villi?
Blood pressure building in the trophoblastic lacunae
What do we call the cytotrophoblast cells that are in contact with uterine tissue in tertiary stem villi?
Outer cytotrophoblast shell
Other name for endometrium?
Decidua tissue
How do the tertiary villi develop? Purpose?
They branch, pushing into the trophoblastic lacunae to increase surface area to increase nutrient transfer => eventually become terminal villi attached to main stem villi
Other name for trophoblastic lacunae after day 21?
Intervillus space
What does the uterine tissue of the tertiary stem villi become after day 21? What is it made of?
Maternal portion of the placenta
Made of decidual cells from the endometrial stroma
What do we call the extraembryonic mesoderm that surrounds the chorionic vessels in the intervillus space?
Chorion = embryonic portion of the placenta
Role of umbilical vein?
Transport blood that has been oxygenated by maternal blood in viili of the placenta to the fetal heart
Role of umbilical arteries? How many of them are there?
Transport blood that has been deoxygenated by the fetus away from the heart and into viili of the placenta
Describe the chorionic blood vessels.
More like blood islands rather than vessels fused with each other to form a vasculature
What keeps the maternal and fetal blood separated in the placenta?
- Cytotrophoblasts
- Syncytiotrophoblasts
- Extraembryonic mesoderm
- Endothelial cells lining capillaries (particularly the fetal ones)
What is the chorion frondosum? Where is it located?
Functional portion of the chorion that surrounds the villi in the placenta
Located at the embryonic pole
What is the chorion laeve? Where is it located?
Portion of the placenta with tertiary villi that broke down => NOT FUNCTIONAL
Located at abembryonic pole
What is the chorion cavity?
Cavity that surrounds the embryo, amniotic cavity, yolk sac, and allantois
When are endometrial cells called decidua cells?
Following implantation, the stromal cells begin to swell as they begin to accumulate lipids and glycogen in the cytoplasm => after swelling the stromal cells are called decidual cells
What are the 2 types of maternal decidual cells of the placenta? Describe each.
- Decidua basalis: portion of the decidua which lies over and associates with the chorion frondosum
- Decidua capsularis: portion of the decidua which lies over the chorion laeve
What are the decidual septa? When do they form? Purpose?
By the third month of pregnancy, portions of the decidua basalis will grow in between the intervillous spaces => formation of the decidual septa, which divide the placenta into compartments called cotyledons
Purpose: they are surrounded and bathed by maternal blood and speed up the exchange of oxygen and nutrients as they allow maternal blood to bathe around the terminal villi and be pushed against them
What is the decidua parietalis?
Part of the uterine lining that is initially separated from the developing embryo but that eventually fuses with the decidua capsularis and the chorionic laeve
What is the chorionic plate?
Extraembryonic mesoderm that lines the chorionic cavity
Describe the maternal arteries that supply the placenta. How are the formed?
Maternal spiral arteries bringing oxygenated and nutrient rich blood to intervillous spaces
PLGF (placental growth factor), secreted by the placenta, stimulates the branching of the spiral arteries, which allows for increased surface area for gas, nutrient, hormone exchange.
What vessels remove wastes and deoxygenated blood from the placenta?
Endometrial veins
Placental blood flow by week 18?
500 mL/min
What are the 3 main functions of the placenta?
- Transport
- Barrier
- Hormone production
Describe the transport function of the placenta.
Allows for the transfer of:
- Gases (O2, CO2, CO)
- Water
- Glucose
- Vitamins
- Lipids
- Hormones
- Electrolytes (NaCl, CaCl2, MgCl2, etc.)
- Maternal antibodies (IgG)
- Drugs and their metabolites
- Waste products
How can maternal stress affect the fetus?
If mom is really stressed out, corticosteroids can pass through the placenta and affect the fetus
Purpose of maternal antibodies crossing the placental membrane? What to note?
Sets up passive immunity against some diseases (i.e. diphtheria, measles, and smallpox)
Note: chicken pox (vericella zoster) and whooping cough (pertussis) are not included in passive immunity!!!
Note: passive immunity is temporary
Describe the barrier function of the placenta. What to note?
Any substance between 50,000 and 100,000 Daltons will be unable to pass through the placenta
Note: unfortunately, most viruses and bacteria, and even some cancers are capable of passing through the placenta (25% of melanomas, leukemias, and lymphomas)
Can Zika pass the placental barrier?
YUP via endocytosis
Can sarcomas pass the placental barrier?
NOPE, but can metastasize to the placenta
What 4 hormones does the placenta produce?
- Human chorionic gonadotropin (hCG)
- Placental growth factor (PLGF)
- Indoleamine 2,3-deoxygenase (IDO)
- Somatomammotropin
Role of indoleamine 2,3-deoxygenase (IDO)?
Destroys tryptophan on maternal T cells leaving them inactive as they approach the placenta, which allows for a foreign body (the fetus) to grow without being attacked by the maternal immune system
Role of somatomammotropin? What to note?
Gives the fetus priority for maternal blood glucose
Note: it can cause gestational diabetes if over-secreted by the placenta
How does transfer occur across the placenta between fetal and maternal blood?
Diffusion or endocytosis
Which cells of the placenta produced hCG?
Syncitiotrophoblasts
Describe the placenta at the end of the 2nd month of pregnancy (10-12 weeks)?
- Decidua parietalis is not yet in contact with the placenta
- Decidua capsularis and decidua basalis are at opposite poles
- Chorionic cavity is shrinking as it is being taken over by the amniotic cavity
- Uterine cavity is still present
Describe the placenta at the end of the 3rd month of pregnancy (15-17 weeks)?
- Chorionic cavity has been taken over by the amniotic cavity
- Decidua parietalis, chorion leaeve, decidua capsularis, and amnion all fuse at the abembryonic pole
- Uterine cavity is very small as it is mainly taken up by the amniotic cavity
What can malformed cotyledons be a sign of? Explain.
Heart defects because a sign that the fetus did not receive adequate oxygenated blood from the mother during pregnancy, so the fetal heart had to work harder to pump less “quality blood” through the developing body, which can result valve defects
What is the amnion made up of? What does it make up? When is it created?
Few layers of epithelial cells derived from epiblast and mesoderm
It is the innermost fetal membrane
Created during the second week of development when epiblast cells migrate toward the embryonic pole and differentiate into a thin membrane to separate the amniotic fluid from the cytotrophoblast
What is amniotic fluid composed of? 4 things. Where does it come from?
- Electrolytes
- Lipids
- Carbohydrates
- Desquamated fetal epithelial cells (have stem cell like properties)
Amniotic fluid mainly comes from the fetal kidneys
How often is amniotic fluid replaced?
Every 3 hrs
Volume of amniotic fluid at week 37?
800-1,000 mL
What are the 6 functions of the amnion?
- Provides a water cushion to protect embryo from impact
- Maintains consistent temperature and pressure
- Allows for free movement of the fetus
- Serves as a barrier to infections
- Allows for symmetrical development of fetus
- Bathes the external areas within the embryo: GIT and lungs with amniotic fluid
Consequence of too little amniotic fluid?
Improper development of lungs and GIT
What is amniocentesis? 4 reasons to perform?
Procedure where amniotic fluid is aspirated with a needle during the 14th-15th week of pregnancy in order perform a biochemical analysis for birth defects
Reasons for amniocentesis include:
- Detect defective enzymes as in Tay-Sachs Disease
- Perform chromosome analysis for genetic diseases such as Down’s Syndrome
- Determine the sex of the fetus
- Detect neural tube defects by measuring levels of alpha-fetoprotein
What would finding alpha-fetoprotein in the amniotic fluid mean?
Neural tube defect
Describe the development of the umbilical cord.
Derived from extraembryonic mesoderm at the posterior end of the bilaminar disc => gives rise to the connecting stalk => angiogenesis in the connecting stalk around week 3 => amnion fuses with the connecting stalk to become the umbilical cord
What are the components of the umbilical cord?
- One fetal vein
- Two fetal arteries
- Wharton’s jelly which encases, protects, and insulates the vessels
- Extraembryonic coelom
- Vitelline duct
- Allantois
What is a Meckel’s diverticulum?
Failure of a portion of the GIT to retract from the umbilical cord during weeks 24-26
Where does embryonic vasculogenesis starts?
Secondary yolk sac and then progresses to surrounding/covering extra embryonic mesoderm
What happens to the chorionic fluid as the amniotic cavity grows?
Diffuses into the amnion
Timing of umbilical cord containing intestinal endoderm connected to the hypoblast of the vitelline duct?
Weeks 6-8
What does Wharton’s jelly contain?
Proteoglycans
Purpose of color Doppler ultrasonogram?
Way of measuring blood flow through the umbilical vessels (both direction and resistance)
Using color Doppler ultrasonogram: are flow velocity waves stronger in the umbilical vein or arteries at week 8? Explain why.
Stronger in the umbilical vein because it is larger and has more blood flowing through it
Describe embryonic vasculogenesis.
- Cells in the extraembryonic mesoderm will cluster and differentiate into angiogenic cell clusters or islands = hemangioblasts
- Hemangioblast cells have two fates which are dependent on the amount of oxygen they are receiving:
a. become blood cells
b. become endothelial cells which line the blood vessels - Hemangioblasts fuse to form the vasculature
Describe the differentiation of hemangioblasts into blood cells.
Internal cells => decreased oxygen (hypoxic) => increased VEGF for adjacent external cells and receive FGFR from adjacent cells => remain in mesodermal or fibroblast tissue state
Describe the differentiation of hemangioblasts into endothelial cells.
External cells => normal oxygen => increased FGFR (fibroblast growth factor receptor) and PLGF released + receive VEGF from internal cells => become endothelial cells
Can color Doppler ultrasonogram measure BP?
NOPE
Describe the color Doppler ultrasonogram at week 12.
Contains an additional wave called the end diastolic velocity (EDV), which suggests increased umbilical arteriole resistance
What is PLGF? How is it different from VEGF?
Placenta growth factor, member of the VEGF family
Eventually the embryo exclusively secretes VEGF to make blood vessels and the EXM in chorion secretes PLGF
How are dizygotic twins formed? Describe their placental membranes.
Ovary releases 2 eggs and each are fertilized by a single sperm
Usually develop 2 seperate placentas, but their chorions can fuse leading to erythrocyte mocaicism = twins express both blood types of their parents (fine though)
How are monozygotic twins formed? Describe their placental membranes.
Derived from one egg and one sperm and have identical genotype
Can occur in 3 ways:
- Embryo splits prior to blastocyst formation => separate amniotic cavities and placentas
- Inner cell mass splits during blastocyst stage => shared placenta and chorionic sac
- Gastrula splits => shared placenta, chorionic sac, and amniotic sac
What are 2 umbilical cord abnormalities?
- Umbilical cord can wrap around the neck of the fetus and cause decrease blood flow to the fetal brain
- False knots are reversible kinks in the umbilical cord and can cause cardiac and vascular defects
What is amniotic banding?
Tears in the amniotic sac, which can cause a limb, finger, head, face to get stuck in it => blood supply will be constricted => potential amputations or craniofacial deformities
What is polyhydramnios? What can it lead to?
EXCESS amniotic fluid => may lead to anencephaly, maternal diabetes, and GI defects
What is oligohydramnios? What can it lead to?
INADEQUATE amniotic fluid (less than 500 ml amniotic fluid) => respiratory or GI defects
3 placental abnormalities?
- Placenta accreta: lack of decidua basalis => chorionic villi attach to the myometrium rather than being restricted within the decidua basalis
- Placenta pecreta: chorionic villi penetrate the myometrium
- Cotyledon malformation
7 consequences of placental abnormalities?
i. Fetal demise
ii. Perinatal distress
iii. Low birth weight
iv. Perinatal asphyxia (low oxygen to fetus)
v. Cognitive abnormalities
vi. Cerebral palsy
vii. Cardiac anomalies (valve disorders + murmurs)
What is pre-eclampsia caused by?
Genetic predisposition and shallow implantation of embryo:
- Flt-1: VEGF receptor on endothelial cells that would participate in placenta formation, also found in blood as sFlt-1
- Placental growth factor (PLGF): binds to Flt-1 to enhance vasculogenesis of extraembryonic mesoderm and branching of maternal spiral arteries only made during pregnancy (during 3rd trimester)
⇒5 week before disease: sFlt-1 rose and PLGF dropped: sFlt-1 in bloodstream hijacks PLGF leading to deterioration of blood vessels in placenta (and liver, kidneys) => placenta does not receive sufficient blood supply, thereby starving the fetus leading to intrauterine growth retardation (IUGR) and associated problems
What is the 2 treatments for pre-eclampsia?
Future treatment: flood mother with PLGF (phase 1 and 2 trials)
Present treatment: early detection to delay premature birth (delivery when appropriate) and parenteral magnesium to prevent convulsions (during labor, delivery, and post-partum)
What are the 9 risk factors for pre-eclampsia?
- First pregnancy
- Overweight
- IVF w/ donor egg
- Women whose mothers or sisters had preeclampsia
- Women carrying multiple babies
- Pre-existing renal disease
- High BP
- Teenage mothers
- Women over 40
What are the 9 symptoms of pre-eclampsia in pregnant women?
- Hypertension
- Proteinuria
- Liver inflammation
- Edema
- Platelet depletion
- Brain swelling, convulsions and possible coma (severe cases) = ECLAMPSIA
- Weight gain
- Changes in vision
- Headaches
Pre-eclampsia incidence?
5% of pregnancies
When are symptoms of pre-eclampsia mostly seen?
3rd trimester
Plasma test for pre-eclampsia?
Decreased levels of VEGF in maternal blood
What is oligohydramnios often due to?
Often due to renal agenesis or amnion leakage
What are anchoring villi?
Placental villi surrounded by cytotrophoblast cells attached to uterine tissue
Risk of miscarriage due to amniocentesis?
~1:300
What is a sarcoma?
Malignant tumor of connective or other nonepithelial tissue
