Placental Structure and Development Flashcards
What is the placenta?
- Exchange organ between the mother and fetues
- Place where the maternal blood interacts indirectly with the fetal blood
- Discoid
- 20-25cm diameter
- 3cm thick
- 400-750g
What is the placenta for?
- Mediates the relationship between the mother and the baby
- Responsible for nourishing and supplying oxygen to the fetus
- Fetal supply line – acts as lungs/GI tract/kidney/liver
- Growth and survival of the fetus absolutely dependent on a healthy, optimally functioning placenta
How is the placenta linked with FGR?
• Affects 5-8% of pregnancies • Baby is pathologically small – hasn’t reached its full growth potential • Consequences of FGR − Iatrogenic pre-term birth − Increased neonatal morbidity − Morbidity and disability − Developmental programming: − Babies born with FGR more likely to suffer from a range of diseases including CVD, obesity, metabolic syndrome, diabetes, schizophrenia − Stillbirth − 1:200 pregnancies − 11/day − >50% still births due to FGR
Causes of FGR • Placental dysfunction − Too small − Abnormal morphology/damage − Impaired placental function = inability to support fetal growth • Placental failure − Inability to support fetal life − Similar to multi-organ failure
Current clinical management
• Screening
− 75% cases FGR missed
− Majority (90%) stillbirths unpredicted
• Current methods of detection
− Ultrasound – best way of diagnosing. However, low risk women only scanned at 20 weeks, and majority of fetal growth happens after
− Symphysio-fundal height –bump measured with tape. Low tech
− Fetal movements – recorded by the mother. Subjective
• Treatment options
− Early delivery
Describe the pre-implantation phase of placental development
- Trophoblast is the first cell lineage to differentiate between the stages of morula and blastocyst
- ICM becomes surrouned by single layer of mononucleated trophoblast surrounding the whole blastocyst
- Later during pregnancy, the trophoblast gives rise to the larger parts of the placenta and fetal membranes, while the iCM gives the embryo, umbilical cord, and placental mesenchyme.
- 6-7 days post conception, the blastocyst hatches from the zona, attaches to the epithelium, and placenta formation begins.
Describe the prelacunar phase of placental development
• Location of the ICM defines the part of the trophoblast that makes the final attachment to the uterine epithelium.
• Only the trophoblasts over the ICM (polar trophoblasts) can lead to implantation
− Rotation of the blastocyst at this stage may lead to failure of pregnancy due to reduced contact of polar TB cells with epithelium
− Varying the orientation of the blastocyst at implantation may result in abnormalities of cord insertion into the chorionic plate
• As soon as the blastocyst has firmly attached to the epithelium, polar trophoblast undergoes syncytial fusion of mononucleated cells to generate the syncytiotrophoblast
• The syncytiotrophoblast invades into the endometrium and covers the blastocyst, so embryonic cells never contact maternal tissue.
− The syncytiotrophoblast is deribed from the cytotrophoblast underneath – these invidual cells proliferate rapidly and fuse.
• At this stage, the pregnancy is invasive and lytic – it erodes the uterine tissue.
Describe the two trophoblast populations that appear during the prelacunar phase.
• Syncytiotrophoblast
− syncytiunm → multinucleates, unicytoplasmic
− Single ‘cell’ forming a continuous layer
− Terminally differentiated, cant proliferate
− Formed by fusion of cytotrophoblasts
• Cytotrophoblast
− Underneath the ST
− Stem cells, proliferate and fuse with overlying ST
Describe the lacunar phase of placental development
• Vacuoles appear in the ST
• They expand and form lacunae, separated by trabeculae → this lacunar system is the beginning of the maternal blood space
• Lacuna formation seperates the trophoblast into 3 layers
− Primary chorionic plate (closest to the blastocyst cavity)
− Lacunar system
− Trophoblastic shell (contacts endometrium)
Cell migration
• Invading syncytiotrophoblast penetrates into interstitium of the endometriym and contacts maternal capillaries
• Erosion of these small vessels leads to the presence of the first maternal blood cells within the lacunae
• The appearance of these blood cells have been equated with the onset of the maternal circulation in the placenta
• 12 days post-conception, implantation is finalized
− Embryo and its surrounding tissue embedded within the endometrium
− ST displays a developmental gradient:
− Thicker under the embryonic pole (site of invasion)
− Thinner towards the aembryonic pole with smaller lacunae
− Extramebryonic mesoderm cells have migrated on top of the inner surface of the CT cells
− Combination of extrambryonic mesoderm and CT is termed chorion
− CTs of the chorionic plate penetrate into the ST mass of the trabeculae, follow their course and reach the maternal side of the placenta by day 15 → first time an embryonic cell other than the ST contacts the maternal tissue.
− These CTs are now called extravillous CTs, and they further invade the endometrial stroma between glands and capillaries
− A subset of these (endovascular trophoblast) reaches and invades the wall of spiral arteries
Describe the development of the villous structures
Primary Villous
• The CT invading day form the primary villous
• Day 13 post conception, trabecular develop their first side branches which may be simple ST protrusions, or may contain a core filled with CT
Secondary Villous
• The mesenchyme cells follow to form the secondary villous
• Extraembryonic mesodermal cells of the chorionic plate follow the CT and penetrate into the trabeculae
• They do not reach the maternal side – leaves the more distal parts filled with CT only
• These parts of the trabeculae are referred to as trophoblastic cell columns, and serve as the proliferating source of the extravillous trophoblast
Tertiary Villous
• Within the mesoderm of the secondary villi, haemangioblastic progenitor cells develop and differentiate
• 20 days post conception, first placental blood cells and endothelial cells develop
• Development of the first placental vessels transforms the villi into tertiary villi
• Tertiary villi accumulate throughout gestation - but villous development occurs particularly in the first and second trimester
Describe how the embryonic and placental circulation are connected
- Complete feto-placental circulation is established 5 weeks post conception
- Occurs by the fusion of the allantois with the chorionic plate
- Chorionic plate vessels fuse with villous capillaries
- You then get the onset of the fetal heart beat
Describe the macroscopic placental anatomy
• Full term placenta is discoid − Diameter 20-25cm diameter − 3cm thick − 400-750g • Considerable variation between placentas
Fetal Surface of the Placenta
• Chorionic plate represents the fetal surface, which is in turn covered by amnion
• Amnion composed of a single layered epithelium, and the amnionic mesenchyme
• Umbilical cord inserts in a slightly eccentric position into the chorionic plate
• Chorionic mesenchyme contains the vessels that are continuous with the vessels of the umbilical cord
• Deriving form the umbilical arteries, the chorionic arteries branch in a centrifual pattern into their final branches, which supply the villous trees
• Chorionic veins are direct continuations of the villous tree veins, and give rise to the single umbilical vein
Maternal Surface of the Placenta
• Basal plate represents the maternal surface
• Artifical surface
• Mixture of fetal extravillous trophoblasts and maternal cells of the uterine decidua
• Also contains ECM, fibrinoid and blood clots
• System of flat grooves subdivide the basal blate into 10-40 elevated regions called lobes – these show a good correspondence with the position of villous trees.
• In a full term placenta, 60-70 villous trees arise from the chorionic plate – so each maternal lobe is occupied by 1-4 villous trees
• At the placental margin, chorionic and basal plates merge, forming the smooth chorion (fetal membranes)
Describe placental regression
- The formation of a discus placenta from the placenta that surrounds the embryo
- The placental ball will regress to form the disc shaped placenta, leaving the fetal membranes
- You have a loss of the placental villi
- Regression is around the umbilical cord – abnormal regression could lead to an abnormal shaped placenta or cord insertion
- This is related to pregnancy pathologies – probably caused by changes in uterine artery blood flow
How does placental development change across gestation?
- Correspond to changes in function
- Early pregnancy → placental growth and development
- Third trimester → efficient nutrient transport and gas exchange
First Trimester
Continuous layer of CT
Extensive CT proliferation and fusion to form ST
Vascularisation begins
Third Trimester
Reduced diameter of vili
Thinning of the ST (from 100um to around 5um)
CTs only cover 20% of the villous structures
Highly vascularised
- In the third trimester, the whole villus is thinner, but particularly the ST → adapted for transfer
- Capillaries are pushed right up against the edge
What are the different types of villous structures present in the third trimester?
- Early in pregnancy, there is just the developing villi
- Fetal lobules (villous trees) arise form the chorionic plate by a thick villous stem derived from the trabeculae
- The branches of the stems continue branching, leading to a large number of stem vili generations
- A few may reach and contact the basal plate → anchoring villi
- The freely floating vili have been divided into 5 types:
Mesenchymal Vili
• 100-250mm diameter
• Forerunners of the intermediate villi
• Found predominantly in the earliest stages of pregnancy – only type present in the developing placenta up to 6 weeks post LMP
• Stromal core is weakly organized and contains large number of mesenchymal cells and developing vessels
Immature Intermediate Vili
• Develop from differentiating mesenchymal villi
• 100-400mm diameter
• Dominate between weeks 8-22
• Further develop into stem vlli by fibrosation of the stroma
• Immature intermediate vili possess a highly characteristic stroma
− Long processes that link together to form matrix-free channels
− Contain large numbers of placental macropahges (Hoffbauer cells)
• Only contain smaller arterioles and venus
Stem Vili
• Derive from the differentiation of immature intermediate vili
• 100-3000mm diameter
• Serve to give mechanical support to the villous tree
• Villous core is characterized by centrally located arteries and veins in a dense, fibrous stroma
• Capillaries are rare – so may not play much part in materno-fetal exchance
• Physiological significance (besides stability) lies in the fact they are surrounded by a perivascular contractile sheath → supports tensile forces within the stem villous blood vessels
Mature Intermediate Villi
• 80-120mm
• Long and slender
• Start to differentiate from mesenchymal vili mid-gestation
• Gently curve and give rise to terminal vili at intervals
• Core is of loose stroma with a few small vessels
Terminal villi
• Length up to 100mm
• Diameter 80mm
• Final branches of the villous trees
• High degree of capillarisation → more than 50% of cross section occupied by vessels
• Makes them the physiological most important components of the villous tree
• Capillaries often dilate into sinusoids covered by vasculo-syncitial membrane with a thickness of 0.5-2mm
− Consists of the ST and endothelium of the capillary separated by basement membrane
• Very efficient for transport as they only have single cell thick capillaries pushing against the ST forming the VSM
What is fetal growth restriction and its proposed causes?
• Fetus doesn’t attain its full growth potential → should have grown bigger if growth inhibiting factors had not been operating in utero
• Head often normally size (head sparing) but lower half is small
• Result of insufficient nutrients cross the placenta as a result of:
− Undernourishment of the mother (common in low income countries)
− Reduced transfer of nutrients across the placenta due to
− Abnormal placental growth and development
− Small or damaged placenta → infarctions common in smokers
− Placental size correlates to fetal weight
What constitutes abnormal growth and development of the placenta?
• Decreased branching of villous trees
• Fewer, smaller terminal vili
• Thicker ST → increased thickness of exchance barrier
• Reduced vascularization
Some of these features to do with placental cell turnover.
Placental cell turnover
• CTs proliferate
• Fuse with the ST
• The ST cells have a finite lifespan (around 30-60 days). They then undergo apoptosis
• When they are dead, they are gathered into syncytial knots
• In FGR, the balance of this normal cell turnover is disrupted
• Normally you have proliferation exceeding apoptosis, in FGR you have reduced cytotrophoblast proliferation and increased apoptosis
• This leads to decreased growth and renewal
− Creates a smaller, less branched placenta
− Unhealthy or damaged ST
− May result in insuffienct nutrient and oxygen supply to the fetus
What are the advantages and disadvantages of using mouse models to study placenta?
Advantages
Ease of genetic manipulation to create disease models
Can study effect of gene knockouts
Relatively cheap
Short gestation
Both have haemochorial placentas (trophoblast bathed in maternal blood)
Disadvantages Some differences to human pregnancy Short gestation Large litters Differences in placental structure
