Chapter 3: Cleavage and Implantation Flashcards
reproductive strategy of invertebrates, sea urchins, amphibians, fruit flies
complete early development as fast as possible
storing a moderate amount of yolk in the oocyte and preproducing much of the molecular machinery
necessary for the embryo to move rapidly through cleavage to the start of gastrulation
produce and store huge amounts of ribosomes and RNA–represent maternal gene products and early development is controlled by maternal genome
reproductive strategy of birds and reptiles
produce very large egg containing enough yolk that early development can proceed at slower pace;
eliminates need for oocyte to synthesize and store large amounts of RNAs and ribosomes before fertilization
reproductive strategies of mammals
eggs are very small; placental eliminates need for a large yolk; mammalian cleavage is prolonged process that typically coincides with the time required to transport early embryo from fertilization site to implantation in uterus
trophoblast
specialized tissue that forms the trophic interface between the embryo and the mother during the cleavage period; placenta ultimately forms from trophoblastic tissue
mammalian cleavage
leisurely process
after 2 cell stage, cleavage is asynchronous with 1 of the 2 cells (blastomeres) dividing to form a 3-cell embryo
morula
embryo with approximately 16 cells
compaction
starting with the 8 cell stage;
individual other blastomeres tightly adhere through gap and tight junctions and lose their individual identity when viewed from the surface
E-cadherin
mediates compaction; calcium-activated cell adhesion molecule; forms a ring around the apical surface of blastomeres
cavitation
process by which through activity of sodium, potassium-adenosine triphosphatase-based system sodium and water move across the outer blastomeres and accumulate in spaces among the inner blastomeres
blastocoel (blastocyst cavity)
the fluid-filled space formed by cavitation
blastocyst
embryo that has a blastocoel;
embryo still surrounded by zona pellucida and has two layers: outer epithelial layer of trophoblast cells and an inner cell mass
represents specialization of blastomeres into two distinct cell lineages
embryonic pole and abembryonic pole
embryonic pole: the end of the blastocyst that contains the inner cell mass
abembryonic pole: opposite end
inner cell mass
give rise to the body of the embryo itself in addition to several extraembryonic structures
trophoblast cells
form only extraembryonic structures, including outer layers of the placenta
fibroblast growth factor-4
growth factor secreted by inner mass cells to maintain mitotic activity in the overlying trophoblast
transition from maternally to zygotically produced gene products
because you don’t have massive storage of maternal ribosomes and RNA, zygotic gene products must come into play at an early stage
most maternal transcription is degraded by two-cell stage ; some of these stimulate activation of embryonic genome which begins to produce RNAs from genes
no short transition between cessation of purely maternal to purely embryonic gene products
epigenetic regulation
mature egg and sperm are transcriptionally inactivated due to methylation which occurs on CpG dinucleotides
does not alter the fundamental DNA sequence
methylation can inactivate informational genes or their regulators
also, different patterns of histone association with chromatin
methylation/demethylation of sperm and eggs
within 4 hours of fertilization, sperm undergo rapid demethylation
demethylation of maternal genome is much more gradual until early morula and remethylation ensues until late blastocyst stage
polarization of blastomeres
polarization of 8 or 16 cell embryo
results in clearly recognizable apical and basal surfaces
results in formation of separate lines of cells-trophoblast and inner cell mass
inside-outside hypothesis
fate of a blastomere derives from its position within the embryo rather than from its intrinsic properties
outer blastomere = trophoblast
inner blastomere = inner cell mass
cell polarity model
if the plane of cell division of a blastomere at the eight-cell stage is parallel to the outer surface of the embryo, the outer daughter cell develops a polarity, with its apical surface facing the zona pellucida;
the inner daughter cell remains apolar and goes onto form part of the inner cell mass
ezrin
actin microfilament-stabilizing protein that is key to a duaghter cell becoming an outer cell; that and also inheriting a patch of outer cell membrane that has microvilli
produce polarity and direct differentiation toward trophoblastic lineage
transformation of trophoblast cells into inner mass cells and vice versa
even when differentiated into these two lineages, before the 32-cell stage, if one cell type is transplanted into the exterior or interior of embryo, it can be transformed into the other cell type
this capability for phenotypic transformation is lost by 32-cell stage
developmental potential or potency
the type of cells that a precursor cell can form;
greater than the cell’s developmental fate
developmental fate
the type of cells that a precursor cell normally forms
not as great as the cell’s developmental potential
Cdx-2
transcription factor critical to formation of trophoblastic cells; essential for trophoblastic differentiation and antagonizes the expression of molecules associated with the inner cell mass
Cdx-2 mutants fail to implant
oct-4
expressed by inner mass cells; codes for specific transcription factor that binds the octamer ATTTGCAT on DNA
close relationship between high expression of oct-4 and highly undifferentiated state of cells
maternally derived oct-4 protein is required to permit development to proceed to the two-cell stage when transcription of embryo begins
expressed in all blastomeres up to the morula stage; expression decreases with increased differentiation
oct-4 is still detected in primordial germ cells as they migrate to genital regions even after expression is ceased in rest of embryo
Sox-2
binds to DNA in partnership with oct-4 to regulate the expression of genes associated with cellular differentiation
Nanog
first appears in the late morula and along with oct-4 functions to maintain the integrity of the inner cell mass
no Nanog, and cells of inner cell mass will differentiate into primitive endoderm
no oct-4 and cells become trophoblast
parental imprinting
expression of certain genes derived from the egg differs from expression of same gens derived from spermatozoon
two female pronuclei: embryo itself will develop normally but the placenta and yolk sac are poorly developed
two male pronuclei: severely stunted embryo whereas placental and yolk sac develop normally
occurs during gametogenesis; methylation is major means of imprinting; imprinted genes are transcriptionally silenced; given imprint is not passed onto the individual’s progeny
sex chromatin (Barr body)
one of the two X chromosomes in the female is inactivated by extreme condensation
purpose: dosage compensation, preservation of cells from excess of X-chromosomal gene product
X-inactivation center
unique locus on X chromosome; initiates X chromosome inactivation
XIST
x-inactive specific transcript
one of the genes in the X-inactivation center; produces large RNA with no protein coding potential
XIST RNA remains in the nucleus and coats the entire inactive X chromosome; in the inactivated X chromosome, the XIST gene is unmethylated and expressed; in active X, XIST is methylated and silent
ontogenetic history of X chromosome inactivation
by the 4-cell stage and into morula stage, the paternally derived X chromosome becomes inactivated as result of paternal imprinting
as embryo forms blastocyst, paternally derided X chromosome in the trophoblast and hypoblast remain inactivated but within cells of inner cell mass both X chromosomes become active
as cells of inner cell mass begin differentiation, the somatic cells undergo random permanent XIST-basted X chromosome inactivation of either maternal or paternal X chromosomes
within germ line, activation of both X chromosomes occurs during the first meiotic division
regulation
the ability of an embryo or organ primordium to produce a normal structure if parts have been removed or added
cell fate not irretrievably fixed and cells can still respond to environmental cues
mosaic development
inability to compensate for defects or to integrate extra cells into a unified whole
fate of cells are rigidly determined, and removal of cells results in an embryo or structure missing components that the removed cells were destined to form
most regulative systems have an increasing tendency to exhibit mosaic properties as development progresses
experimental techniques to show regulative properties
- separate blastomeres of early cleavage-stage embryos and determine whether each one can give rise to an embryo; can do this for up to 4 cell embryos
- single cell from an early cleavage-state embryo can be injected into the blastocoel of a genetically different host
chimeras or mosaics
cells from one early cleavage-state embryo injected into another early embryo; it becomes incorporated into host embryo
donor cell can be identified by histochemical or cytogenetic analysis
fate mapping
they allow one to follow the pathways along which a particular cell can differentiate
totipotent
retain the ability to form any cell type in the body; retained at 8-cell stage
tetraparental or hexaparental organisms
combine blastomeres of different embryos; form a single large embryo which goes on to become a normal-appearing animal (mouse)
human chimeras
human genetic mosaics; most commonly recognized when some regions of the body are male and others are female
result of fusion of two early fraternal twin embryos
also could be result of exchange of cells through common vascular connections
body axes in embryo
conflicting evidence; some suggest that second polar body establishes at least one axis
early mammalian embryo is a highly regulative system and that boxy axes do not become fixed until the end of cleavage or early gastrulation
deletion or ablation experiments
removing part and determining the way that the remainder of the embryo compensates for the loss
addition experiments
adding a part and determining the way that the embryo integrates the added material into its overall body plan
one of the most powerful experiments is injecting a genetically or artificially labelled cell into a blastocyst cavity of the host embryo; or using the marking to determine the developmental potency of the donor cells
transgenic embryos
commonly mice; produced by directly injecting foreign DNA into the pronuclei of zygotes
knock out
now common to knock out gene to study its function in normal development
can also use coding RNAi (RNA interference): knocks down rather than blocking gene expression
conjoined twins
The separation of portions of an embryo is sometimes incomplete, and although two embryos take shape, they are joined by a tissue bridge of varying proportions; extent of bridging varies between embryos
parasitic twins
a form of conjoined twins in which an a much smaller but remarkably complete portion of body protrudes from body of an otherwise healthy and normal host twin
common attachment regions: oral, mediastinum and pelvic
Bateson’s rule
when duplicated structures are joined during critical developmental stages, one structure is the mirror image of the other
stem cells
cells in both human adults and embryos that have the ability to develop into a variety of cell and tissue types in response to specific environments; can be induced to differentiate
in adults, found in bone marrow, skeletal muscle, brain tissue and fat
express oct-4, Sox-2, and Nanog to maintain undifferentiated state
embryonic stem cells or embryonic germ cells
stem cells found in embryo; derived from inner cell mass or germ cell lineage
induced pluripotent stem cells
from adult somatic cells; characteristics of embryonic stem cells induced in these adult cells and they revert back into an undifferentiated state capable of differentiating into a wide variety of tissues if induced to do so
cloning
fusing or introducing an adult cell or nucleus into an enucleated oocyte and allowing the hybrid cell to develop into an embryo and ultimately to mature into an adult.
early pregnancy factor
a molecule of the heat shock protein family and homologous to chaperonin 10 (an intramitochonodrial protein); immunosuppressant and thought to provide immunological protection to the embryo
produced by embryo and found in serum secreted by ovary; detectable in maternal blood 36 to 48 hours after fertilization
zona pellucida and corona radiata during cleavage
corona radiata lost within two days of cleavage
zona pellucida remains until implantation in the embryo
zona pellucida prior to implantation
composition of zona changes, facilitating transport and differentiation of embryo
blastocyst hatching
process by which embryo begins to shed zona pellucida when entering the uterus;
a small region of the zona pellucida, usually directly over the inner cell mass, dissolves, and the blastocyst emerges from the hole
trophectodermal projections
long microvillous extensions protruding from surfaces of trophoblastic cells;
in rodents, release cysteine proteases enzymes that assist in blastocyst hatching; then make contact with endometrial epithelial cells as the process of implantation begins
functions of zona pellucida
- promotes maturation of the oocyte and follicle
- zona pellucida serves as a barrier that normally allows only sperm of the same species access to the egg
- initiates acrosomal reaction
- after fertilization, modified zona prevents any additional spermatozoa from reaching zygote
- during early stages of cleavage, acts as porous filer through which certain substances secreted by the uterine tube can reach the embryo
- lacks histocompatibility antigens, serves as immunological barrier for embryo
- prevents blastomeres of early embryo from dissociating
- facilitates differentiation of trophoblastic cells
- normally prevents premature implantation of the cleaving embryo in the wall of the uterine tube
uterus at implantation
even before actual contact is made between embryo and endometrium, uterine epithelium secretes into uterine fluid certain cytokines and chemokines that facilitate the implantation process
dissolution of zona pellucida signals the embryo is ready for implantation
implantation stage 1
attachment of expanded blastocyst to the endometrial epithelium
surface of endometrial epithelium cells display various adhesion molecules on their surface that allow implantation to occur only during a narrow 20-24 day window of cycle
leukemia-inhibiting factors (LIF) on endometrial surface and LIF receptors on the trophoblast during implantation
implantation occurs above inner cell mass at the embryonic pole
implantation stage 2
penetration of uterine epithelium
cellular trophoblast undergoes more differentiation
formation of syncytiotrophoblast
small projections of syncytiotrophoblast insert themselves between the uterine epithelium and spread along the epithelial surface of basal lamina that underlies endometrial epithelium to form flatted trophoblastic plate
invasion is enzymatically mediated; site is first marked by a bare area or a noncellular plug and is later sealed by migrating uterine epithelial cells
cytotrophoblast
in area around inner cell mass cellular trophoblast cells
syncytiotrophoblast
fusion of cytotrophoblast to form this multinucleated tissue; will soon surround the entire embryo
highly invasive tissue; erodes its way to endometrial stroma
trophoblastic plate
flattened projections of syncytiotrophoblast that spread along the epithelial surface of basal lamina of endometrium
end up penetrating basal lamina
implantation stage 3
projections from the invading syncytiotrophoblast envelop portions of maternal endometrial blood vessels; erode vessel walls and maternal blood begins to fill the isolated lacunae that have been forming in the trophoblast
trophoblast is not as invasive anymore
decidual cells
decidual reaction
fibroblastlike stromal cells of edematous endometrium begin to swell with accumulation of glycogen and lipid droplets
tightly adherent and form massive cellular matrix that first surrounds implanting embryo and later occupies most of the endometrium (DECIDUAL REACTION)
primary function of decidual reaction is to provide the immunologically privileged site to protect the developing embryo from being rejected
interleukin-2
secreted by leukocytes that have infiltrated he endometrial stroma during the late progestational phase ; prevents maternal recognition of embryo as foreign body during early stages of implantation
miscarriage
spontaneous abortion; occurs mostly during first 3 weeks of pregnancy; often not recognized by mother at this point
many aborted embryos are highly abnormal, with most common being chromosomal abnormalities
ectopic pregnancy
implantation that occurs in an abnormal site
tubal pregnancies
most common type of ectopic pregnancy; found in ampullary portion of tube, can be located anywhere from fibriated end to the uterotubal junction
common in women who have had endometriosis, earlier surgery, or pelvic inflammatory disease
endometriosis
condition characterized by the presence of endometriumlike tissue in abnormal locations
ovarian and abdominal pregnancies
rare; can be result of fertilization of ovum before it enters the tube;; reflux of fertilized egg from the tube, or penetration of tubal pregnancy from the tube
rectouterine pouch (pouch of Douglas)
most common implantation site of abdominal pregnancy; located ehind the uterus
lithopedion
calcified remains of an ectopic pregnancy embryo that is not delivered
placenta previa
if the embryo implants too close to the cervix, the placental partially covers the cervical canal; causes bleeding in later pregnancy and can cause the death of mother or fetus if untreated due to bleeding associated with premature placental detachment
