Early Foetal Development Flashcards by Dean Whaley

How do you measure Fertilisation age?

measured from the time of fertilization (assumed to be +1 day from last ovulation)
difficult to know time of fertilization exactly (unless IVF)

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How do you measure Gestational Age?

Determined by fertilization date (+14 days) if known, or early obstetric ultrasound and comparison to embryo size charts.

Calculated from the time of the beginning of the last menstrual period

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How do you calculate the Carnegie stage?

23 stages of embryo development based on embryo features not time
Allows comparison of developmental rates between species
Covers the window of 0-60 days fertilization age in humans

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What are the periods of the first Trimester?

Embryogenic stage

Embryonic stage

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Which period forms the second & third trimester?

Fetal stage

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What happens in the embryogenic stage?

14-16 days post-fertilization):
establishing the early embryo from the fertilized oocyte

Determining two populations of cells: pluripotent embryonic cells (contribute to fetus)

Extraembryonic cells (contribute to the support structures eg placenta

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What happens in the Embryonic stage?

Establishment of the Germ layers & differentiation of tissue types.

Establishment of the body plan

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What happens in the Fetal stage?

Major organ systems now present
Migration of some organ systems to final location
Extensive growth and acquisition of fetal viability (survival outside the womb)

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What happens in the first few days of life?

Ovulated oocyte fertilised by sperm, forms zygote.

Zygote undergoes a series of cleavage divisions, giving a 2, 4 ,8 (cleavage embryos).

8 Cell embryo proceeds with further mitotic divisions giving us the Morula (16+ cells).

Morula progresses to form Blastocyst (200-300 cells).

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What is happening genetically at the 4 -8 cell stage?

Embryo is dependent on maternal mRNAs and proteins to get through the first divisions

These mRNA and proteins are synthesized and stored during oocyte development (i.e. pre-ovulation)

Failure to synthesise, store or interpret these mRNAs and proteins during oogenesis can impair embryonic development.

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What happens in the Maternal to zygotic transition?

Transcription of embryonic genes (zygotic genome activation)
Increased protein synthesis
Organelle (mitochondria, Golgi) maturation

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What happens during compaction?

Around the 8-cell stage or later:
Outer cells become pressed against zona
Change from spherical to wedge-shaped.

Outer cells connect to each other through tight gap junctions and desmosomes
Forms barrier to diffusion between inner and outer embryo
Outer cells become polarised

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What cell types are created by compaction?

Inner cell & outer cell. Outer cells form shell of blastocyst, inner cells form clump at inner blastocyst

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What is the role of the Zone Pellucida?

Hard protein shell inhibiting polyspermy and protects early embryo

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What do the inner cell mass in the blastocyst give rise to?

Pluripotent embryonic cells that will contribute to the final organism

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What do the outer cells (Trophoectoderm) in the blastocyst give rise to ?

Extra-embryonic cells that contribute to the extraembryonic structures that support development

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What is the Blastocoel?

Fluid-filled cavity formed
osmotically by
trophoblast pumping
Na+ ions into cavity

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What happens in Hatching?

Hatching (day 5-6):
To implant the blastocyst must escape zona pellucida.
Enzymatic digestion
Cellular contractions

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What happens 7-9 days post implantation in the Trophectoderm lineage?

Trophoectoderm lineage separates further:

trophoblast cells fuse to form syncitiotrophoblast

Syncitiotrophoblast invasion destroys local maternal cells in the endometrium

Creates interface between embryo and maternal blood supply

cytotrophoblast cells remain individual to provide source of syncitiotrophoblast cells

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What happens to the inner cell lineage at days 7-9?

Inner cell mass separates further into:

epiblast: from which the fetal tissues will be derived.
hypoblast: which will form the yolk sac (extraembryonic structure)

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When does Bi-laminar embryonic disc formation occur?

day 12

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What happens in Bi-laminar embryonic disc formation?

final stage before gastrulation

Some cells become separated from the epiblast by the formation of a new cavity – the amniotic cavity.

These amnion cells will contribute to the extra-embryonic membranes.

This leaves a two-layer disc of epiblast and hypoblast, sandwiched between cavities.

Embryo is now ready for gastrulation

What underpins pregnancy testing?

Syncitiotrophoblast secretes hCG

Detection of beta hCG subunit in blood/urine is basis of pregnancy testing

What happens at day 15?

at 15 days - thickened structure forms in the midline of the epiblast (Primitive streak)

Primitive streak defines body axis, cranial + caudal, left + right sides of embryo.

Primitive node contains primitive pit, forms groove

epiblast cells migrate inwards towards streak, detach from epiblast and slip beneath it into embryo anterior - invagination

What happens at day 16?

16 - Hypoblast cells are replaced by a new layer known as a definitive endoderm, remaining cells of epiblast are known as the ectoderm. some of the epiblast cells that had migrated previously under the epiblast form the mesoderm once formation of layers is complete epiblasts no longer migrate towards primitive streak

What do the cells of the Endoderm Give rise to?

GI Tract, Liver, Pancreas, Lung, Thyroid

What do the cells of the Ectoderm give rise to?

CNS + Neural crest Skin epithelia Tooth enamel

What do the cells of the Mesoderm give rise to?

Blood Muscle Gonads, Kidneys, adrenal cortex Bone, cartilage

What is the first major event after Gastrulation?

Notochord is a rod-like tube structure formed of cartilage-like cells Forms along the embryo midline, under the ectoderm Day 13

What is the role of the Notochord?

Acts as a key organizing centre for neurulation and mesoderm development

How do the neural folds form?

Notochord signals direct the neural plate ectoderm to invaginate forming neural groove Creates two ridges (neural folds) running along the cranio-caudal axis Neural crest cells specified in neural folds

How is the neural tube formed?

Neural folds move together over neural groove Ultimately neural folds fuse, forming a hollow tube Neural tube overlaid with epidermis (ectoderm) Migration of the neural crest cells from folds

When does neural tube closure occur?

Neural tube initially open at each end Closure at head end: ~ d23 Closure at tail end: ~ d27

Why is neural tube closure important?

Closure at head end precedes formation of brain structures

What are some failure of neural tube closure development defects?

Anencephaly (absence of most of the skull and brain) arises from failure to close at the head end (1/10,000 births) Spina bifida (open neural tube at birth, usually lower spine due to failure to close tail end– varying severity – (0.4-5/1000 births)

Where do neural crest cells come from?

Ectoderm-derived, plastic and migrate extensively during development:

How do we classify Neural crest cells?

Cranial NC: cranial neurones, glia, lower jaw, middle ear bones (ossicles), facial cartilage Cardiac NC: aortic arch/pulmonary artery septum, large arteries wall musculoconnective tissue Trunk NC: dorsal root ganglia, sympathetic ganglia, adrenal medulla, aortic nerve clusters, melanocytes Vagral & Sacral NC: parasympathetic ganglia and enteric nervous system ganglia

What do neural crest migration failures lead to?

Defects of neural crest migration/specification lead to diverse birth defects including pigmentation disorders, deafness, cardiac and facial defects and failure to innervate the gut.

What is somitogenesis?

Formation of somites, segmentation of the body axis

What are somites?

arise from paired blocks of paraxial mesoderm flanking the neural tube and notochord

How does Somitogenesis take place?

Blocks of paraxial mesoderm condense and bud off in somite pairs One of each pair either side of the neural tube. Somitogenesis commences at the head end and progresses down the long axis of the embryo Rate of ‘budding’ or appearance of somite pairs is species-specific, as is the number of pairs. Humans 1 pair/90 min, 44 pairs

When does human somitogenesis end?

When we have reached 44 pairs

What are the types of tissue that somites divide into?

Sclerotome | Dermomyotome

What does the Sclerotome develop into?

Vertebrae + Rib cartilage

What does the Dermomyotome develop into?

in turn sub-divides to form: Dermatome: gives rise to dermis of the skin, some fat and connective tissues of neck and trunk Myotome: forms the muscles of the embryo

What is the yolk sac?

Embryonic structure involved in early Haematopoesis. Derived from hypoblast

How does the primitive gut form?

The primitive gut arises from two types of folding in the embryo: Ventral folding: where the head and tail ends curl together Lateral folding: where the two sides of the embryo roll This pinches off part of the yolk sac.

What is the primitive gut further organised into?

Foregut Midgut Hindgut

What does the Foregut give rise to?

esophagus, stomach, upper duodenum, liver, gallbladder, pancreas

What does the Midgut give rise to?

Lower duodenum & remainder of small intestine, ascending colon & first two thirds of transverse colon

What does the Hindgut give rise to?

Last third of the transverse colon, descending colon, rectum & upper anal canal

How does the Heart develop?

Begins as tube of mesoderm around day 19, beating and pumping blood commences around day 22 Fetal heartbeat detectable from ~6 weeks gestational age

How do the lungs develop?

Arise from the lung bud, and endodermal structure adjacent to the foregut, in the 4th week of development Lung bud splits into two at the end of the 4th week, and progressively branches through development

How do the Gonads develop?

Forms from mesoderm as bipotential (i.e. not committed to testis or ovary) structures known as gonadal/genital ridges XY embryos: presence of SRY gene on Y chromosome directs gonadal cells to become Sertoli cells, triggering testis development, Leydig cell formation and testosterone production XX embryos: absence of SRY leads to gonadal cells adopting a granulosa cell fate and ovary development, requires reinforcement by FOXL2