Download Conceptus – anything developed from fertilized egg

Fertilization and pre-implantation
Endometrium – uterine lining moderated by female hormones, sloughed off and recreated
in the menstrual cycle.
Two distinct phases:
Proliferative phase – regenerates endometrium lost, regulated by estrogen
Secretory phase – endometrium thickens, regulated by progesterone
- ovulation occurs between two phases with follicular development
- Corpus luteum is created in ovary from remnant follicle after ovulation, it secretes
progesterone for about 14 days post-ovulation (underlying constant in menstrual cycles),
the loss of progesterone results in the sloughing off of endometrium and thus the cycle
repeats.
- fertilization occurs in the fallopian tube and travels towards the uterus, secreting Early
Pregnancy Factor. Blastomeres begin dividing rapidly into a 12 to 32 blastomere
structure called a morula. Compaction is the result of the blastomeres remaining tightly
bound to one another as they divide. At this point
the conceptus enters the uterus.
- After more divisions, a central cavity is formed
called the blastocoel, and the conceptus is now
referred to as a blastocyst, containing the inner
cell mass/embryoblast and the trophoblast. The
zona pellucida begins to break down and
implantation occurs.
Implantation – Week 1
After contact with the endometrium, the trophoblast differentiates into 2 distinct layers:
Cytotrophoblast – maintains cellularity, less specialized
Syncytiotrophoblast – specialized multinucleated cytoplasmic mass external to
blastocyst
- erodes endometrium allowing the conceptus to burrow into the endometrium
- begins to produce human chorionic gonadotropin (hCG) which prevents
corpus luteum degeneration preserving the endometrium, after sometime it takes
over progesterone production thus corpus luteum is not necessary after that point
- decidual reaction surrounding implanted embryo creates decidual cells for
nourishment and immunological protection for the conceptus
- further immunological protection is provided by little recognizable antigen on
syncytiotrophoblast surface
- eventually expands into maternal capillaries in endometrium, creating blood
filled lacunae network. Cytotrophoblast develops into primary chorionic villi
extending into the syncytiotrophoblast,
secondary villi develop around week 2
Bilaminar Disc – Week 2
Embryoblast differentiates into the Bilaminar Disc around day 14:
Hypoblast – small layer of cells form on the blastocoel side of the embyroblast
Epiblast – remainder of embryoblast in which the majority of fetus is created
Disc separates amnionic cavity
(epiblast side, proliferate into amnioblasts and form amnion) and primary yolk
sac/exocoelomic cavity/ primary umbilical vesicle (hypoblast side, where blastocoel
used to be)
Amniotic fluid - maintains temperature, provides hydraulic support, allows movement,
does NOT provide nutrient support. Creates a hydraulic wedge in birth canal for infant.
Hypoblast migrates down the outer membrane to form another layer called exocoelomic
membrane surrounding the exocoelomic cavity. Exocoelomic cells produce a layer of
connective tissue called extraembryonic mesoderm. The mesoderm expands creating
two layers with a fluid filled extraembryonic ceolom in the middle.
The splanchnic mesoderm surrounds the yolk sac and the somatic mesoderm coats the
interior wall of the cytotrophoblast and the epiblast. As the layers separate further apart,
the connecting stalk in the somatic mesoderm keeps it connected to the cytotrophoblast,
it eventually becomes the umbilical cord.
With signaling from the hypoblast, epiblastic cells proliferate and push the hypoblast
cells outward, eventually pinching off the exoceolomic membrane. This pinching then
forms the secondary yolk sac/ secondary umbilical vesicle and the exocoelomic cyst.
Finally the prechordal plate forms at the future cranial end as a thickening of the
hypoblast.
Trilaminar Disc – Week 3
Gastrulation – the formation of the germ layers which are:
Ectoderm – epidermis, central and peripheral nervous systems, eye, inner ear, connective
tissue of the head as neural crest cells.
Mesoderm – ALL skeletal muscles, blood cells and blood vessels, all visercal smooth
muscle coats, serosal linings of all body cavities, ducts and organs of the reproductive
and excretory systems, most of the cardiovascular system. The trunk contains mesoderm
derived connective tissue such as cartilage, bones, tendons, ligaments, dermis, and stroma
of internal organs.
Endoderm – epithelial linings of respiratory and gastrointestinal tracts, and glandular
cells of associated organs such as the liver or pancreas.
The primary chorionic villi now cover make up much of the surface of the
cytotrophoblast and begin branching forming the secondary chorionic villi. Tertiary
chorionic villi are formed as the mesenchyme cells form definitive arteriocapillary
networks that becomes a part of fetal circulation. The cytotrophoblast also grows out to
becomes the cytotrophoblastic shell surrounding the chorionic sac and attaching to the
endometrium. On the exterior of the shell, anchoring stem chorionic villi grow outward
with terminal branch chorionic villi extending from them.
The chorion now consists of outer structures of the trilaminar disc, the extraembryonic
mesoderm, cytotrophoblast, and syncytiotrophoblast, and creates the chorionic/
extraembryonic coelom. Eventually separates into villous chorion in the placenta and
the smooth chorion surrounding the fetus. Eventually, the amnion will grow out to the
border of the smooth chorion and eliminate the extraembryonic coelom. Three decidual
layers are formed during development:
Decidua basalis – endometrium between placenta and uterus
Decidua capsularis – endometrium expanding with the fetus and eventually disintegrates
Decidua parietalis – remainder of endometrium not involved with fetus, smooth chorion
eventually fuses with this layer as it fills the uterus
At the caudal end opposite the prechordal plate, the primitive streak is formed by the
proliferation of cells on the median plane at the dorsal/epiblastic aspect. The streak
elongates by proliferation of cells at the caudal end, pushing it towards the cranial end
forming a primitive node at the cranial most end.
As this occurs, the primitive groove forms as an indentation along the cell mass up to the
primitive pit in the primitive node. These are both formed as mesenchyme cells
migrates from these indentations into the area between the epiblast and hypoblast.
At this point several structures have arisen. At the end of gastrulation, the remaining
epiblast becomes the embryonic ectoderm, the migrating mesenchyme becomes the
notochord and embryonic mesoderm, and the mesenchyme that displaced the hypoblast
becomes the embryonic endoderm. The prechordal plate becomes the oropharyngeal
membrane and a similar clocoal membrane forms at the caudal end. Both of these
membranes will eventually be the only places where mesoderm will not invade, and will
become the mouth and anus respectively.
As the mesenchyme migrates through the primitive groove and pit, the notochordal
process is formed from the migration of these cells from the pit to the prechordal plate.
The primitive pit actually follows in creating a canal like structure, the notochordal
canal, which is a tube that extends from the prechordal plate to the primitive node. The
underlying embryonic endoderm fuses and degenerates with the anterior aspect of the
notochordal canal, creating a flat notochordal plate. The cells in the plate proliferate
and fold in to become the notochord and the endoderm grows back in place. The
notochord is responsible for defining the longitudinal axis and provides signals to
develop the axial musculoskeletal structures and central nervous system, as well as
contributing to the intervertebral discs.
As the notochord forms, the allantois grows out of the caudal edge of the umbilical
vesicle into the connecting stalk. The mesoderm form this structure will form blood
vessels to the placenta and be part of the future umbilical cord.
The remaining mesoderm grows medial to lateral, creating 3 distinct mesodermal areas:
Paraxial Mesoderm – forms first somites by the end of 3rd week, develops into axial
skeleton, some muscles/CT in trunk and some in limbs and part of skin
Intermediate Mesoderm – urinary and reproductive systems
Lateral Mesoderm – CT of body wall and CT and musculature of GI tract.
The lateral mesoderm becomes further divided by the formation of the intraembryonic
ceolom which extends from the lateral regions to the cranial tip (resembling a horseshoe).
The somatic mesoderm and adjacent ectoderm form the somatopleure and the
splanchnic mesoderm and adjacent endoderm form the splanchnopleure. The
intraembryonic ceolom will eventually divide into three body cavities by the second
month, the pericardial cavity, the pleural cavities, and the peritoneal cavity.
As the notochord forms, it induces the overlying embryonic ectoderm to thicken and form
the neural plate, which will eventually give rise to the central nervous system. The plate
broadens and grows with the notochord. About halfway through the week, a depression
occurs along the cranial-caudal axis called the neural groove, lateral to which are the
neural folds. These neural folds are prominent at the cranial end and are the first signs
of brain development. At the end of the third week, the neural folds begin to grow
together over the groove to form the neural tube, eventually to become the CNS. The
neural crest is formed over the neural tube from nearby neuroectodermal cells losing
their epithelial attachment and separating into two pieces just dorsal to the neural tube.
The neural crest develops sensory ganglia of spinal and cranial nerves, as well as
autonomic ganglia.
The primordial heart and the pericardial coelom are formed between the septum
transversum and the oropharyngeal membrane. The septum transversum is the tissue
connecting the primordial heart to the edge of the embryonic disc; it eventually forms the
central tendon of the diaphragm just inferior to the mediasteinum.
Embryo Folding and Structure Development
Folding occurs in the 4th week in both the median plane and the horizontal plane
In the median plane, the head and caudal regions move ventrally. The forebrain region
folds superior over the primordial heart as the heart moves ventrally. The septum
transversum then moves caudally into position where the future diaphragm will be. As
the folds occurs, part of the umbilical vesicle moves up into the region becoming the
foregut. The stomodeum is a pocket of the amnion in between the forebrain and the
primordial heart.
The caudal eminence grows just inferior to the caudal membrane. As it folds over the
caudal membrane, a similar pulling of the umbilical vesicle occurs forming the hindgut
the terminal portion of which form the clocoa, the primordium of the bladder and rectum.
With this folding, the allantois gets pulled into the embryo.
Lateral folding is induced by the rapidly growing somites and spinal cord from neural
crest cells. The ventrolateral walls grow dorsally towards the median plane. A part of
the umbilical vesicle gets pulled in with this folding, becoming the midgut. The midgut
is separated from the remaining umbilical vesicle by the omphaloenteric duct. At the
end of this process, the amnion is reduced to a small communicating portion ventrally as
part of the umbilical cord. The lateral folding eventually eliminates the communication
between the intraembryonic and extraembryonic coelom and isolates part of the midgut.
The midgut is then attached to the embryo by the dorsal mesentery of the endoderm.
The somatopleure interior of the lateral folding now becomes the lateral abdominal
walls.
The diaphragm is composed of mainly the septum transversum, posteriorly surrounding
the aorta and esophagus is from the dorsal mesoesophagus, lateral to which are the
pleuroperitoneal membranes. The body wall fills in the gap around the diaphragm
completing the structure.
Cellular Signaling
Fibroblast Growth Factors – FGFs work primarily on FGF Receptors, which are types
of tyrosine receptor kinases. They can induce many different signaling pathways, and are
important for angiogenesis, axon growth, and mesoderm differentiation.
Hedgehog Proteins – This family consists of three hedgehog genes, Sonic, Desert, and
Indian hedgehogs. Sonic hedgehog is involved with a multitude of events including limb
patterning, neural tube formation, somite differentiation, gut regionalization and others.
These proteins bind to Patched and activate it, allowing the inhibited protein Smoothed
to transduce the necessary signal.
WNT Protiens – WNT receptors originate from the frizzled family of receptors, and are
involved in limb patterning, midbrain development, and some aspects of somite and
urogenital differentiation.
TBFβ – this superfamily contains important proteins such as bone morphogenic
proteins, transforming growth factor βs, activin proteins, and Mullarian inhibiting
factor. These proteins are important for extracellular matrix formation and epithelial
branching in lung, kidney, and salivary gland development. The BMP family induces
bone formation and regulates cell division, migration, and death by apoptosis.
Myoblasts from the somite mass extend to the developing heart, pulling nerve fibers with
it. Septum transversum begins to grow inferiorly pulling nerves with it as well and
becoming the diaphragm. The diaphragm is composed of mainly the septum
transversum, extension of the body wall, and a small potion the mesentery of esophagus,
and small areas in between septum and body wall extensions are from the pleuropericardial segments
Activin (-like) – released by hypoblastic cells
Bone morphogenic protien, Fibroblastic growth factors – released by endoderm
Chordin, Noggin, Follistatin – released by notochord