Early Fetal Development

Question 1

What are the 3 ways of measuring time in embryo-fetal development?

Answer 1

1. Fertilization age (also known as conceptual age) - measured from the time of fertilization (assumed to be +1 day from last ovulation). Problem is difficult to know time of fertilization exactly (unless IVF)
2. Gestational age - calculated from the time of the beginning of the last menstrual period (LMP). Determined by fertilization date (+14 days) if known, or early obstetric ultrasound and comparison to embryo size charts.
3. 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.

Question 2

What is the embryogenic stage?

Answer 2

14-16 days post-fertilization. Involves establishing the early embryo from the fertilized oocyte. Two populations of cells determined: pluripotent embryonic cells (contribute to fetus). Extraembryonic cells contribute to the support structures eg placenta.

Question 3

What is the embryonic stage?

Answer 3

16-~50 days post fertilization. Establishment of the germ layers and differentiation of tissue types. Establishment of the body plan.

Question 4

What is the fetal stage?

Answer 4

~50 to 270 days post-fertilization or ~8 to ~38 weeks. Major organ systems now present. Migration of some organ systems to final location. Extensive growth and acquisition of fetal viability (survival outside the womb).

Question 5

Describe the development of zygote over first few days of life

Answer 5

Ovulated oocyte is fertilised to form a zygote. Zygote then goes through cleavage stage, undergoing mitotic divisions from 2 cells to 8 cells. A 16 cell+ morula is then formed and finally blastocyst contains 200-300 cells.

Question 6

How do initial zygotic divisions occur?

Answer 6

Until 4-8 cell stage, the genes of the embryo are not transcribed. 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.

Question 7

What happens in the maternal to zygotic transition?

Answer 7

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

Question 8

What is the role of compaction?

Answer 8

Compaction starts the formation of the first two cell types. Around the 8-cell stage or later, outer cells become pressed against zona. Cell 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.

Question 9

What parts does the blastocyst contain?

Answer 9

1. Zona Pellucida: Hard protein shell inhibiting polyspermy and protects early embryo.
2. Inner cell mass: Pluripotent embryonic cells that will contribute to the final organism.
3. Trophoectoderm: Extra-embryonic cells that contribute to the extraembryonic structures that support development.
4. Blastocoel: Fluid-filled cavity formed osmotically by trophoblast pumping Na+ ions into cavity.

Question 10

What is hatching?

Answer 10

To implant the blastocyst must escape zona pellucida.

Does this through enzymatic digestion and cellular contractions.

Question 11

What happens to trophoectoderm during peri-implantation events?

Answer 11

Trophoectoderm lineage separates further:

1. Trophoblast cells fuse to form syncitiotrophoblast
2. Syncitiotrophoblast invasion destroys local maternal cells in the endometrium
3. Creates interface between embryo and maternal blood supply
4. cytotrophoblast cells remain individual to provide source of syncitiotrophoblast cells

Question 12

What happens to inncer cell mass during peri-implantation events?

Answer 12

Inner cell mass separates further into:

1. Epiblast: from which the fetal tissues will be derived.
2. Hypoblast: which will form the yolk sac (extraembryonic structure)

Question 13

What is the bi-laminar embryonic disc formation?

Answer 13

The bilaminar (two-layer) embryonic disc is the 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.

Question 14

Why is hCG used in pregnancy testing?

Answer 14

Syncitiotrophoblast secretes hCG so detection of beta hCG subunit in blood/urine is basis of pregnancy testing.

Question 15

What organs does the endoderm give rise to?

Answer 15

GI Tract, Pancreas, Liver, Lung, Thyroid

Question 16

What organs does the ectoderm give rise to?

Answer 16

CNS and neural crest, skin epithelia, tooth enamel

Question 17

What does the mesoderm give rise to?

Answer 17

Blood (endothelial cells, red and white blood cells), Muscle (smooth, skeletal and cardiac), gonads, kidneys, adrenal cortex, bone, cartilage

Question 18

What is the notochord and when does it form?

Answer 18

Day 13 onwards. Notochord is a rod-like tube structure formed of cartilage-like cells. Forms along the embryo midline, under the ectoderm. Acts as a key organizing centre for neurulation and mesoderm development.

Question 19

How are neural folds fomed during neurulation?

Answer 19

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

Question 20

How is the neural tube finally formed during neurulation?

Answer 20

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

Question 21

What precedes formation of brain structures?

Answer 21

Neural tube is initially open at each end. Closure at head end occurs around day 23 and closure at tail end around day 27. Closure at head end precedes brain development.

Question 22

What occurs if neural tube closure doesn’t happen properly?

Answer 22

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

Question 23

What are neural crest cells and what do different ones form?

Answer 23

Ectoderm-derived, plastic and migrate extensively during development

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

Question 24

What can defects of neural crest cause?

Answer 24

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.

Question 25

Define somitogenesis and somite

Answer 25

Somitogenesis: formation of somites
Somites: arise from paired blocks of paraxial mesoderm flanking the neural tube and notochord

Question 26

How does somitogenesis start?

Answer 26

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.

Question 27

What two tissues do somites initially form?

Answer 27

Sclerotome: vertebrae and rib cartilage

Dermomyotome, which 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

Question 28

What happens on day 16 of embryonic development and how?

Answer 28

Formation of the gut tube. The primitive gut arises from two types of folding in the embryo:

1. Ventral folding: where the head and tail ends curl together.
2. Lateral folding: where the two sides of the embryo roll.

Question 29

What do gut foldings cause and give rise to?

Answer 29

Folds pinches off part of the yolk sac to form the primitive gut. Primitive gut is then patterned into foregut, midgut and hindgut.

Question 30

What are the derivatives of the primitive gut?

Answer 30

Foregut: esophagus, stomach, upper duodenum, liver, gallbladder, pancreas
Midgut: lower duodenum and remainder of small intestine, ascending colon and first two-thirds of transverse colon
Hindgut: last third of the transverse colon, descending colon, rectum and upper anal canal

Question 31

How does the heart arise?

Answer 31

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

Question 32

How do the lungs arise?

Answer 32

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.

Question 33

How do the gonads arise?

Answer 33

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.