Embryology Flashcards
What are the processes in embryology?
Growth - occurring by increase in cell numbers, increase in size of cells or increase in volume of extracellular matrix
Differentiation - of stem cells into specialist cell types
Cell migration - some cells move a long way from their origin
Cell death - hollowing our rods of tissue into tubes for example
What happens in fertilisation?
Ovulation - an ovum is released from the ovarian follicle and swept up into the oviduct by cilia and muscle contractions of oviduct
- Fertilization normally occurs in the wide ampulla of the oviduct - sperm have travelled from the upper vagina, through the uterus, into the oviduct
- The sperm penetrates the cumulus oophorus, corona radiata and zona pellucida around the ovum, then the membranes of the sperm and ovum fuse
- Ovum completes meiosis
• The male and female pronuclei fuse, bringing 46 chromosomes together
briefly, before the first round of cell division starts
What is contraception?
Contraception is deigned to prevent fertilisation, either physically preventing contact between sperm and egg, physically blocking implantation, or hormonally reducing egg and sperm production.
Physical blocks include barrier methods (eg: condoms, diaphragm); intrauterine devices to block sperm or prevent embryo implantation; surgical methods (vasectomy in men; tubal ligation or blocking in women)
Hormonal methods: female contraceptive pill (oestrogen and/or progestin inhibits ovulation); male pill (synthetic androgen reduces sperm production); emergency contraceptive pills: high dose progestin or hormone blocker initiates menstruation
What is infertility?
Around 15% couples experience fertility problems
Male infertility: too few sperm or poor motility; normal ejaculate is 2-6ml with 20-100 million sperm per ml - anything less may cause problems
Female infertility: blocked oviducts following pelvic inflammatory disease; hostile cervical mucus; immunity to sperm; absence of ovulation, etc.
What is assisted reproduction?
• IVF (in vitro fertilization) or ICSI (intracytoplasmic sperm injection)
• In IVF: gonadotrophins given to stimulate ovary; oocytes are collected
laparoscopically
• sperm are added to egg; 8 cell stage embryo placed in uterus
• IVF - 30% successful after first attempt in younger couples
FF: Formation of the morula
• Rapid cell division (cleavage) begins immediately: 1st division occurs within 24h; 2nd division occurs within 48h; 6-12 cells by 3 days: morula (‘mulberry’)
• Day 4 - morula undergoes compaction – tight junctions form between cells
• 2 sets of cells become distinct:
inner cell mass (embryoblast) – will form embryo
outer cell mass (trophoblast) – will form part of placenta
FF: formation of the blastocyst
- Day 4-5 - fluid enters the ball of cells – morula transformed into hollow blastocyst
- Inner cell mass lies at the embryonic pole of the blastocyst
FF - implantation
- Day 6: blastocyst ‘hatches’ from the zona pellucida – and begins to implant in the endometrium (in its secretory phase - growing under influence of progesterone from the corpus luteum)
- Trophoblast cells secrete human chorionic gonadotrophin (hCG) – maintains uterine lining
- hCG levels high enough to be detected by end of 2nd week - basis of pregnancy tests
- The implanted embryo employs mechanisms to suppress immune system and block recognition as foreign tissue – so it’s not attacked by mother’s immune system
What is failure of implantation?
I • 10% blastocysts though to fail to implant
• Around 15% of detected pregnancies miscarry - but true figure for
miscarriage is closer to 50%
• Abnormalities in blastocyst include absent embryoblast - trophoblast may
develop into hydatidiform mole (which may miscarry or be detected in
routine US scan)
• Many human embryos (>70%) contain major chromosomal abnormalities
(from IVF studies) - embryonic signalling disrupted, causing uterine stress
response - implantation less likely (Brosens et al. 2014)
• This ‘natural screening’ reduces the rate of birth defects
• Some embryos with chromosomal abnormalities do implant - antenatal tests
are available for various genetic defects; advances in genetics and the scope of screening present ethical dilemmas for individuals and society as a whole
What is an ectopic pregnancy?
• Blastocyst implants in abnormal site, eg: peritoneal cavity, oviduct
• Most ectopic embryos die in 2nd month – causing haemorrhage; ruptured
oviduct may require emergency surgery.
What happens in week 2?
• Trophoblast differentiates into TWO layers: cytotrophoblast & syncytiotrophoblast
• Embryoblast differentiates into TWO layers: epiblast & hypoblast (bilaminar germ disc)
• The original blastocyst cavity is lined with hypoblast cells – becomes the yolk sac cavity – facing the hypoblast
• Some yolk sac cells form a new layer: the extraembryonic mesoderm
• TWO brand new cavities form: amniotic cavity within epiblast & chorionic
cavity within extraembryonic mesoderm
• The extraembryonic (chorionic) cavity expands until the embryo is suspended
by a stalk of extraembryonic mesoderm: the connecting stalk (precursor of
the umbilical cord)
• Uteroplacental circulation starts - lacunae in syncytiotrophoblast open into
large capillaries (sinusoids) in endometrium
Week 3 - gastrulation
• Primitive streak appears in week 3
• Establishes longitudinal axis and bilateral symmetry of embryo
• Epiblast cells proliferate and migrate through the primitive streak:
gastrulation
• 3 germ layers formed: ectoderm, mesoderm, endoderm - forming the
trilaminar germ disc
• Mesoderm cells migrate through the primitive pit to form the notochord
(replaced later by vertebral column)
Week 3 : Buccopharyngeal and cloacal membranes
• Depressions visible on ectoderm - where ectoderm tightly fused to endoderm
• Later become the blind ends of the gut tube
• Buccopharyngeal membrane will perforate in week 4 to form opening of
mouth
• Cloacal membrane will perforate in week 7 to become openings of anus and
urogenital tracts
Week 3: genes and fate maps
- The differentiation of regions is governed by expression of genes, eg: cerberus in head region, Nodal in primitive streak
- The fate of gastrulating epiblast cells can be mapped by cell tracing studies
Week 3: gastrulation and teratogenesis
• Gastrulation may be disrupted by genetic abnormalities and toxic insults
• High doses of alcohol can kill cells in anterior midline of germ disc – affecting
face and brain development
• Situs inversus – transposed thoracic and abdominal viscera – often associated
with organ defects
• Caudal dysgenesis – insufficient caudal mesoderm leads to abnormal lower
limbs (sirenomelia), kidneys, etc
• Sacrococcygeal teratomas – from persistent remnants of primitive streak,
most common tumours in newborn (1 in 37,000)
Week 3 : what are the fates of germ layers?
Germ layers will give rise to adult tissues & organs:
• Ectoderm forms epidermis & nervous tissue
• Mesoderm forms skeletal, muscular & circulatory systems & connective
tissues
• Endoderm forms digestive & respiratory tracts
Week4 : ectoderm
• The notochord secretes substances including noggin and chordin which inhibit the growth factor BMP-4, causing the overlying ectoderm cells form the neural plate or neurectoderm
• In week 4, the flat neural plate rolls up into the neural tube
• The neural tube will form the brain and spinal cord
• Other ectoderm (in the presence of BMP-4) becomes epidermis
• The otic and lens placodes are thickenings of ectoderm that will form the
labyrinth of the ear and the lens of the eye
• Ectoderm also gives rise to subcutaneous glands, pituitary gland and tooth
enamel
Week 4: mesoderm
• Mesoderm condenses into 3 columns on each side
• Paraxial mesoderm forms paired segments: somites - appear in a
craniocaudal sequence; ‘segmentation clock’ depends on cyclic expression of
several genes in mesoderm
• Each somite divides into: sclerotome; myotome; dermatome; molecular
signals from neural tube and notochord (sonic hedgehog and noggin) induce
sclerotome to differentiate
• Intermediate mesoderm forms urogenital structures
• Lateral plate mesoderm pulls apart at the edges of the germ disc - to form a
visceral/splanchnic layer lining yolk sac/organs and a parietal/somatic layer
lining inside of body wall
• Growth of somites causes lateral folding of the embryo and encloses
intraembryonic cavity
Week 4: endoderm
• Development of the brain causes cephalocaudal folding of the embryo – encloses part of the endoderm-lined cavity inside the embryo as the primitive gut tube
• Foregut finishes blindly at buccopharyngeal membrane
• Midgut still attached to yolk sac (outside the body of the embryo) via yolk sac
duct/vitelline duct
• Hindgut finishes blindly at cloacal membrane
What are the consequences of embryonic folding?
- Flat trilaminar germ disc converted into cylinder of nested endoderm, mesoderm and ectoderm tubes
- Brings ectoderm to cover the outside of the body – encloses endoderm, mesoderm and intraembryonic cavity
- Pulls the amniotic cavity around the developing embryo – and pushes the connecting stalk and vitelline duct together to form the umbilical cord
What are the functions of extra embryonic membranes?
- to store or remove waste products
- to transport nutrients
- to exchange gases (supply oxygen, remove carbon dioxide)
- to create an aquatic environment for the developing embryo
What are extraembryonic membranes in placental mammals?
• Amniotic cavity develops early, in epiblast
• Yolk sac forms but contains no yolk platelets – only fluid
• Allantois grows and fuses with chorion, forming the fetal part of the
placenta (allantoic vessels in reptiles and birds are equivalent to umbilical
vessels in placental mammals)
• The placenta functions to transfer oxygen and nutrients to fetus, and
remove carbon dioxide and metabolic waste
• The placenta also produces hormones (hCG then progesterone) to
maintain the uterine lining and oestriol to stimulate growth of uterus and breasts
Week 2 of development of formation of placenta
• From day 9, small cavities called lacunae form in the syncytiotrophoblast -
and at the same time, maternal capillaries are enlarging to form sinusoids
• Around day 12, the lacunae and sinusoids join up and the uteroplacental
circulation is established; at the same time, extraembryonic mesoderm is forming, and cavitating to create the extraembryonic (or chorionic) cavity - which expands until the embryo is suspended by its connecting stalk of extraembryonic mesoderm
• The extraembryonic mesoderm lining the inside of the cytotrophoblast is also known as the chorionic plate
Week 4 development of placenta
• Lacunae have expanded and and cytotrophoblast has grown to form
fingerlike villi - and an outer cytotrophoblast shell
• Stem or anchoring villi reach from chorionic plate out to the
cytotrophoblast shell; free villi branch from the stem villi
• Primary chorionic villi are protrusions of cytoptrophoblast
• Secondary chorionic villi contain an extraembryonic mesoderm core
• Tertiary stem villi contain capillaries within the mesoderm core
• Lacunae grow larger - forming intervillous spaces, full of maternal blood
supplied by spiral arteries
Week 8 development of placenta
• The chorion around the attachment of the umbilical cord becomes more
bushy - chorion frondosum; the chorion opposite the embryo becomes
smooth - chorion laeve
• The endometrium is now called the decidua (as it will be shed at birth): the
decidua basalis is in contact with chorion frondosum; the decidua capsularis encloses the implanted embryo; the endometrium elsewhere is called the decidua parietalis
• Cytotophoblast layer progressively lost from many villi - so the barrier between metal blood and maternal blood is just the endothelium of the villous capillary and a thin layer of syncytium; placenta brings fetal and maternal blood very close – but no mixing of blood
• Villi produce large surface area for exchange of gases, nutrients, wastes between maternal and fetal blood
• Some cytotophoblast cells incorporate themselves into the walls of the maternal spiral arteries - increasing their diameter and lowering their resistance.
