Placenta Structure and Function Flashcards
Routes of Exchange
(Nutrients and Waste)
- nutrients must feed both the fetus and placenta
- Some molecules cross the placenta & reach the fetus unchanged
- Some are utilised by placenta & broken down before passing to fetus.
- Some molecules are modified by the placenta for the fetus.
- Placenta may also prevent the passage of certain molecules.
Chorionic Villus
reversed roles of vessels:
- umbilical vein carries oxygenated Blood–> fetus & umbilical artery carries deoxygenated blood & waste mother
Two Ways molecules cross to fetus
- Histotrophic: ‘uterine milk’ secreted by endometrium, often maintained by progesterone
- Trophoblast either absorb material or engulf via phagocytosis
- Long period in ungulates since implantation is later (day 35- horse, 15-20- ruminants, cf: 7- man)
- Pinocytosis (ingestion of liquid into a cell by the budding of small vesicles from the cell membrane) persists in later pregnancy in pig/horse/carnivores via areolae & sheep/carnivores via endometrial glands and haemophagous zones (areas of RBC update for Fe)
- Haemotrophic: Direct transfer between bloodstreams by ‘definitive’ placenta
Factors affecting rate of Exchange
- Specific transport mechanisms for individual nutrients
- Vascular dynamics (type of vessel, rate of flow, diffusion distance)
- Placental utilization
- Surface area
- Concentration gradient
Mecahnisms of Exchange
- Simple diffusion- Very small, or very lipid soluble species
- Ions (Na+, K+, Cl-), Fatty acids, cholesterol, fat soluble vitamins, steroids (small MW), Urea, uric acid, creatinine & gases
- Facilitated diffusion- For less soluble molecules, often needed in large amount e.g. glucose.
- Requires higher M:F gradient & uses glucose transporters:
- On trophectoderm- GLUT1+= assymetrically located on the surface closest to maternal epithelium. Maternal epithelium contains GLUT1, GLUT3, GLUT4, SGLT to drive the glucose to the fetus
- 1/3 of glucose is used by placenta, most of which is converted –>lactate –>fetus
- Oxygen diffusion- Oxygen diffuses freely across the placenta & rapidly reaches an equilibrium between maternal & fetal haemoglobin. This equilibrium is exploited by the fetus in 4 ways:
- Fetal haemoglobin has a ↑ oxygen affinity
- Fetal blood contains ↑ haemoglobin
- Fetus-to-mother loss of CO2 enhances O2 transfer.
- Mother-to-fetus loss of O2 ↑ maternal affinity for CO2 & ↓ fetal affinity for CO2
- Active transport- Requires energy & conc. can be higher either side. All other molecules, which are:
- Potentially toxic: Fe2+, I-, Ca2+, phosphate
- Lipid insoluble: amino acids, water soluble vitamins
- Needed to maintain gradients: Na+, K+, Cl
- IgG: humans (receive most) >> carnivores >> ungulates (binding proteins)
- Includes amino acids as concentration higher in fetal blood
- Special: Iron Uptake
- Uptake of transferrin ( iron-binding blood plasma glycoproteins) in humans & rodents via transferrin receptors
- Progesterone dependent secretion of uteroferrin from endometrial glands in mare
- Carnivores seppage of maternal RBCs taken up by trophoblast- heme sourced from RBCs
Protection from Trauma and Tertogens
1. Physical protection: The fetal membranes, especially the amnion & associated fluid-cushion
2. Teratogens: external influences that induce developmental abnormalities (toxic or pathogens):
- Micro-organisms - especially viruses (cross with ease, particularly with haematogenous exchange)
- Radiation
- Nutritional deficiencies- selenium & vit E deficiencies major developmental issues
- Hyperglycaemia
- Chemicals:
Non-iatrogenic (eg environmental pollutants, diet/lifestyle – alcohol, smoking, LSD);
Iatrogenic (administered for treatment- thalidomide, tetracyclines & chemotherapeutics)
- Exposure during embryonic period–> major malformations as CNS, heart & limbs & genitalia are forming
Placenta/Fetus= Foreign
(Immunological Protection)
Trophoblast express MHC Class I
A major gene that helps determine self to non - self: MHC!!!
Imprinting in the placenta: either the mother or fathers allele is silenced in protein production-MHC class I: this one is co-dominantly expressed from alleles of BOTH parents
- “Paternal alloantigens” = MHC class I alleles that are co-dominantly –> expressed ‘semi-allogenic’
- Express both polymorphic (v. different to other individuals) & non-polymorphic (similar to other’s) MHC
- Can also be H-Y antigens (male fetus) and minor histocompatibility complex
- The placenta and fetus can be foreign!!–> “semi-allogenic tissue”- half mother/half father
- Antigen specific toleration! Tolerating the antigens of the mouse she is pregnant with!
-pregnancy restricitve
MAternal Immune System modulation
- Specific: directed against paternal alloantigen–> tolergenic response
- Non-specific: general “dampening” of the immune system- change in cytokine mileu–> more suppressive cytokines (↑ IL-10, IL-4 & ↓IFN gamma)
Placental Interactions
- Trophoblast cells express very few trophoblast specific antigens & no MHC Class II –>‘invisible’ to IS
- Trophoblast cells–> chemicals that modulate local immune response (e.g. IDO–> ↓ T cell proliferation)
Implications- dampening of maternal IS–> ↑ susceptibility to infections (e.g. toxoplasmosis) & may respond differently to treatments
Progesterone
Source:
- *CL only:** Bitch, alpaca, camel, goat, queen, rabbit, sow
- *Horse:** early CL, placenta days 70-100
Sheep: early CL, 50 days
Cow: CL + placenta 6-8 months
Function: Inhibits follicular development & ovulation, ↓ myometrium contractility, Stimulates endometrial glands secretions, Immunosuppressant, Mammary gland development
Extra Info: Horses: as progesterone ↓, a metabolite of it (DHP) ↑
Chrionic Gonadotrophin
Source:
- Human (hCG) by syncytiotrophoblast
- Horse (eCG) by endometrial cups
Function:
- Luteotrophic (human) & stimulates follicular growth & ovulation in equids.
- Used therapeutically in non-equids to mimic LH/FSH- long half-life (6 days)
Extra:
Not present in ruminants, carnivores & pigs
Oestrogen
Source:
- Follicles, CL, placenta & fetal gonads
- Horse: early follicles, late FG & placenta
- Cow & sheep: placenta (+ ovary)
- Pig: placenta
Function:
- Growth of myometrium,
- Proliferation of endometrium
- & Stimulates uterine blood flow
- Horse oestrogens (from urine) used in human replacement therapy
Extra:
- Generally peaks late in pregnancy. Can be conjugated or unconjugated - affects activity
Placental Lactogens
Source:
- Placenta in primates, rodents, ruminants (by binucleate cells)
Function:
- Alters carbohydrate & protein metabolism,
- aids mammary development & luteotrophic
Extra:
Not present in carnivores, equids, pigs. Have arisen from duplications of PRL or GH genes
Relaxin
Source:
- Placenta: horse, dog, cat
- CL: pig, rat
- Endometrium: guinea pig
- Ovary: relaxin related peptide- ruminant
Function:
Relaxation of pelvic ligaments, Expansion of birth canal, Helps maintain myometrial quiescence, Cervical ripening, Mammary gland development
Concentration highest in late pregnancy- as the fetus is getting larger
Placenta
Key requirements of fetus during development: physical protection, blood supply & protection from mother’s IS
Placenta
- formed by the apposition of maternal & fetal tissue for the purposes of physiological exchange
- Connected to body of embryo by a vascular supply= chorionic villus, the functional unit of the placenta
Fetal Membranes
- Four types in mammals: Chorion, yolk sac, amnion & allantois
- Fetal membranes, like the embryo are derived from zygote, genetically = half maternal & half paternal
- Their main functions are to isolate & protect the fetus & to form the placenta(s/e).
Development of Fetal Membranes
- Blastocyst= Inner cell mass with trophoblasts around outside.
ICM: Primitive endoderm–> yolk sac
Mesoderm–> amniotic sac.
- Chorion= composed of trophoblasts & one layer of mesoderm.
- Allantois= outpouching from embryo’s primitive gut, makes its way towards the chorion & eventually fuses with it –> allantochorion).
- In domestic mammals the yolk sac is replaced by a chorioallantoic placenta (the mare forms a chorioviteline placenta)- transitory
Horse Fetal Membrane
- Type: Choriovitelline –> chorioallantoic
- Shape of points of villous contact: diffuse
- Implantation: centric (superficial)
- Cell layers: Epitheliochorial (6 layers)
- Interdigitation at attachment pts: villous
Ruminants: Fetal Membrane
Type: Chorioallantoic
Cotyledonary
Centric Implantation (central)
Epitheliochorial (6 layers)
villous interdigitation
Pig: fetal membrane
- Chorioallantoic fetal Membrane
- Diffuse
- Centric (superficial) implantation
- Epitheliochorial (6-layers)
- Folded interdigitation
Dog and Cat Fetal Membrane
- Choriovitelline–> Chorioallantoic
- zonary
- Eccentric
- Endotheliochorial (4 layers)
- Lamellar interdigitation
Human Fetal Membrane
- chrioallantoic
- Discoid
- Interstitial (invasive)
- Haemochoral (2-3 layers)
- Villous interdigitation
Two Types of Placenta
- Choriovitelline- yolk sac makes contact with uterine wall & is the main site of exchange- v. primitive - seen in marsupials & non-mammals. Can be seen in some domestic species but only transitory
- Chorioallantoic- main point of exchange & development of chorionic villus is via the allantochorion
Types of Villous Contact
- *1. Discoid (human, rodents)
2. Cotyledonary (Ruminants)** - *3. Zonary (cats and Dogs)
4. Diffuse (horse, sow)**
6 Cell Layers
- Fetal endothelium
- Fetal connective tissue
- Chorionic epithelium
- Uterine Epithelium
- Maternal connective tissue
- Maternal endothelium
If four layer (endotheliochorial): maternal endothelium, chorionic epithelium, fetal connective, fetal endothelium
Species Diff
(Pig)
- Blastocyst expansion–> elongation of the blastocyst, which goes on to form the diffuse epitheliochorial placenta of the pig.
- The tips of the chorioallantois= avascular & become necrotic.
- Blastocyst expands with fluid uptake which ensures it makes diffuse contact with the uterine wall
- Areolae- special regions of chorioallantoic membrane into which the maternal glands–> histotrophic secretions in response to progesterone (nutrition from its mother in the form of uterine secretions, known as histotroph)
SPECIES DIFF
(horse)
- Day 21: Choriovitelline placenta
- Day 24: allantochorion begins outpouching
- Day 50: chorioallantoic
- Umbilical cord has an amniotic portion & an allantoic portion
- Main placenta has microcotyledons= microscopic
- Chorioallantois extends even into the non-pregnant horn- hence why horses can’t carry twins (not enough surface area for exchange)
- Chorionic girdle: band of trophoblast cells on placenta- highly invasive- detach & migrate down endometrial gland & implant deeply into uterus forms the endometrial cups which produce eCG
Species Diff.
(ruminants)
- Site of exchange= Placentome: fetal cotyledon (chorionic villus located here) + maternal caruncle
- Sheep caruncle- concave (bovine is convex) & has specialised haemophagous region to facilitate iron uptake
- Binucleate trophoblast cells: Cells start on the fetal side–> migrate down –>embed in the epithelium- close to maternal blood vessels, where they produce placental lactogens which pass –>maternal blood
Species diff:
Carnivores
- Lamellae- sheets of interlocking fetal & maternal tissues–> ↑ SA for exchange
- Zonary placenta- the band is where the chorionic villus are:
- Transfer zone is where most of the nutrient exchange is going on.
- Pigmented zones are specialised to pick up iron (hence black colour)
