Purinergic enzymes on extracellular vesicles: immune modulation on the go
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Фев. 15, 2024
An
increase
in
the
extracellular
concentration
of
ATP
as
a
consequence
cellular
stress
or
cell
death
results
activation
immune
cells.
To
prevent
inflammation,
is
rapidly
metabolized
to
adenosine,
which
deploys
an
anti-inflammatory
signaling
cascade
upon
binding
P1
receptors
on
The
ectonucleotidases
necessary
for
degradation
and
generation
adenosine
are
present
membrane
many
cells,
their
expression
tightly
regulated
under
conditions
inflammation.
discovery
that
vesicles
(EVs)
carry
purinergic
enzyme
activity
has
brought
forward
concept
EVs
new
player
regulation.
Adenosine-generating
derived
from
cancer
cells
suppress
anti-tumor
response,
while
mesenchymal
stem
contribute
restoration
homeostasis
after
infection.
Here
we
will
review
existing
knowledge
containing
enzymes
molecules,
discuss
relevance
these
modulation
potential
therapy.
Язык: Английский
Extracellular vesicles secreted by human aneuploid embryos present a distinct transcriptomic profile and upregulate MUC1 transcription in decidualised endometrial stromal cells
Human Reproduction Open,
Год журнала:
2024,
Номер
2024(2)
Опубликована: Янв. 1, 2024
Abstract
STUDY
QUESTION
Do
extracellular
vesicles
(EVs)
secreted
by
aneuploid
human
embryos
possess
a
unique
transcriptomic
profile
that
elicits
relevant
response
in
decidualized
primary
endometrial
stromal
cells
(dESCs)?
SUMMARY
ANSWER
Aneuploid
embryo-derived
EVs
contain
transcripts
of
PPM1J,
LINC00561,
ANKRD34C,
and
TMED10
with
differential
abundance
from
euploid
induce
upregulation
MUC1
transcript
dESCs.
WHAT
IS
KNOWN
ALREADY
We
have
previously
reported
IVF
secrete
can
be
internalized
ESCs,
conceptualizing
successful
implantation
to
the
endometrium
is
facilitated
EVs.
Whether
these
may
additionally
serve
as
biomarkers
ploidy
status
unknown.
DESIGN,
SIZE,
DURATION
Embryos
destined
for
biopsy
preimplantation
genetic
testing
aneuploidy
(PGT-A)
were
grown
under
standard
conditions.
Spent
media
(30
μl)
collected
(n
=
175)
140)
at
cleavage
(Days
1–3)
stage
187)
142)
blastocyst
3–5)
stage.
Media
samples
n
35
cleavage-stage
pooled
order
obtain
five
four
pools.
Similarly,
blastocysts
create
one
pool.
ESCs
obtained
women
undergoing
diagnostic
laparoscopy.
PARTICIPANTS/MATERIALS,
SETTING,
METHODS
isolated
pools
centrifugation
EV-RNA
sequencing
was
performed
following
single-cell
approach
circumvents
RNA
extraction.
(estradiol:
10
nM,
progesterone:
1
µM,
cAMP:
0.5
mM
twice
every
48
h)
incubated
24
h
(50
ng/ml).
on
ESCs.
MAIN
RESULTS
AND
THE
ROLE
OF
CHANCE
less
abundant
fragments
originating
genes
PPM1J
(log2fc
−5.13,
P
0.011),
LINC00561
−7.87,
0.010),
ANKRD34C
−7.30,
0.017)
more
1.63,
0.025)
compared
embryos.
Decidualization
per
se
induced
downregulation
−0.54,
0.0028)
prerequisite
establishment
receptive
endometrium.
The
expression
significantly
increased
treatment
embryo-secreted
0.85,
0.0201).
LARGE
SCALE
DATA
Raw
data
been
uploaded
GEO
(accession
number
GSE234338).
LIMITATIONS,
REASONS
FOR
CAUTION
findings
study
will
require
validation
utilizing
second
cohort
EV
samples.
WIDER
IMPLICATIONS
FINDINGS
discovery
differs
supports
possibility
develop
non-invasive
methodology
PGT-A.
dESCs
embryo
proposes
new
mechanism
underlying
failure.
FUNDING/COMPETING
INTEREST(S)
supported
Marie
Skłodowska-Curie
Actions
fellowship
awarded
SM
European
Commission
(CERVINO
grant
agreement
ID:
79620)
BIRTH
research
Theramex
HQ
UK
Ltd.
authors
no
conflicts
interest
declare.
Язык: Английский
Gene expression changes in blastocyst hatching affect embryo implantation success in mice
Frontiers in Cell and Developmental Biology,
Год журнала:
2025,
Номер
13
Опубликована: Фев. 6, 2025
In
mammalian
embryonic
development,
blastocyst
hatching
is
essential
for
normal
implantation
and
development
of
the
fetus.
We
reported
previously
that
blastocysts
out
zona
pellucida
(ZP)
exhibited
site
preferences
were
associated
with
pregnancy
outcomes.
To
characterize
these
differences,
we
analyzed
transcriptomes
in
following
developing
mouse
within
16
h
hatching:
expanding
(E),
from
A-site
(A),
B-site
(B),
C-site
(C),
hatched
(H),
non-hatching
(N).
By
principal
component
analysis
hierarchical
cluster
analysis,
determined
gene
expression
profiles
A
B
blastocysts,
which
resulted
good
fertility,
clustered
closely.
C
N
poor
closely,
but
distantly
B.
Embryos
at
B-
vs.
C-sites,
pregnancy,
showed
178
differentially
expressed
genes
(DEGs),
mainly
involved
immunity,
correlated
positively
birth
rate.
These
DEGs
primarily
regulated
by
transcription
factors
TCF24
DLX3.
During
hatching,
immune-related
regulated,
such
as
Ptgs1,
Lyz2,
Il-α,
Cfb
(upregulated)
Cd36
(downregulated).
immunofluorescence
staining,
found
C3
IL-1β
on
extra-luminal
surface
trophectoderm
blastocyst,
suggesting
they
play
a
role
maternal-fetal
interactions.
As
developed
to
fully
state,
307
either
upregulated
factor
ATOH8
or
downregulated
SPIC
switch
immune
pathways.
Based
outcome,
identified
three
patterns
complex
changes
transcriptional
regulation
network
failed
successfully
blastocysts.
LASSO
regression-based
model
using
Cd36,
Cfb,
Cyp17a1
predict
success.
This
study
revealed
diverse,
multidimensional
developmental
fates
during
short-term
indicated
properties
embryo
had
major
effect
suggest
their
preimplantation
affect
implantation.
contributes
our
understanding
Язык: Английский
Blastocoel fluid RNA predicts pregnancy outcome in assisted reproduction
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 11, 2025
Abstract
Background
and
objective
Assessing
embryo
quality
objectively
with
greater
precision
remains
a
key
challenge
in
assisted
reproductive
technologies
(ART).
RNA
molecules
excreted
by
the
are
detectable
spent
media
(ESM)
blastocoel
fluid
(BF).
Their
potential
for
predicting
pregnancy
outcome
is
however
unknown.
The
aim
of
study
was
to
determine
whether
can
serve
as
biomarkers
predict
ART.
Material
methods
primary
this
multicenter
develop
prediction
model
implantation
based
on
mRNA
ESM
BF.
We
included
255
couples
undergoing
ART
single
transfers
between
2018
2019
four
IVF
clinics
Sweden.
BF
were
collected
from
individually
cultured
embryos.
extraction
performed
using
our
novel
protocol
developed
To
identify
signature,
each
sample
underwent
sequencing
(Smart-seq3),
followed
differential
gene
expression
analysis.
A
machine
learning
(ML)
approach
applied
genes
input
data
create
results
measured
positive
or
negative
urine
human
chorionic
gonadotropin
(hCG)
test
result
14
days
after
transfer.
Results
After
pre-processing
controls,
we
105
cleavage
stage
230
blastocyst
embryos
75
In
total
identified
345
1132
respectively
1157
There
significant
difference
abundancy
108
(p-value<0.05;
fold
change
+2/-2)
hCG
but
not
ESM.
Consequently,
selected
train
different
ML
models
most
optimal
combined
L2
Regularized
Logistic
Regression
differentially
abundant
feature
principal
component
analysis
preprocessing.
predicted
sensitivity
83%
specificity
59%
(AUC
76%
accuracy
69%).
Testing
an
independent
subset
9
samples,
training
dataset,
demonstrated
60%,
75%,
67%
result.
Conclusion
For
first
time,
demonstrate
that
be
comprehensively
mapped
individual
samples
highly
sensitive
isolation
protocol.
Moreover,
used
approach.
Our
has
enhance
selection,
thereby
improving
success
rate
treatment.
future,
larger
clinical
trials
needed
validate
robustness
method
compare
it
against
standard
care.
Язык: Английский
Multi-omics of extracellular vesicles: An integrative representation of functional mediators and perspectives on lung disease study
Frontiers in Bioinformatics,
Год журнала:
2023,
Номер
3
Опубликована: Фев. 9, 2023
Extracellular
vesicles
are
secreted
by
almost
all
cell
types.
EVs
include
a
broader
component
known
as
exosomes
that
participate
in
cell–cell
and
tissue–tissue
communication
via
carrying
diverse
biological
signals
from
one
type
or
tissue
to
another.
play
roles
messengers
of
the
intercellular
network
mediate
different
physiological
activities
pathological
changes.
In
particular,
most
natural
carriers
functional
cargo
such
DNA,
RNA,
proteins,
thus
they
relevant
advancing
personalized
targeted
therapies
clinical
practice.
For
application
EVs,
novel
bioinformatic
models
methods
based
on
high-throughput
technologies
multi-omics
data
required
provide
deeper
understanding
their
biomedical
characteristics.
These
qualitative
quantitative
representation
for
identifying
markers,
local
cellular
inference
tracing
origin
production
distant
organ
reconstruction
targeting
influential
microenvironment
transferable
activators.
Thus,
this
perspective
paper
introduces
context
provides
an
integrative
viewpoint
state
current
research
applications.
Язык: Английский
From Germ Cells to Implantation: The Role of Extracellular Vesicles
Journal of Developmental Biology,
Год журнала:
2024,
Номер
12(3), С. 22 - 22
Опубликована: Авг. 23, 2024
Extracellular
vesicles
represent
a
large
heterogeneous
class
of
near
and
long-distance
intercellular
communication
mediators,
released
by
both
prokaryotic
eukaryotic
cells.
Specifically,
the
scientific
community
has
shown
growing
interest
in
exosomes,
which
are
nano-sized
with
an
endosomal
origin.
Not
so
long
ago,
physiological
goal
exosome
generation
was
largely
unknown
required
more
investigation;
at
first,
it
hypothesized
that
exosomes
able
to
remove
excess,
reject
unnecessary
constituents
from
cells
preserve
cellular
homeostasis.
However,
thanks
recent
studies,
central
role
regulating
emerged.
Exosomes
act
as
vectors
cell–cell
signaling
their
cargo,
proteins,
lipids,
nucleic
acids,
influence
pathological
processes.
The
findings
on
widespread
spectrum
biomedical
applications
diagnosis
prognosis
therapies.
In
this
review,
we
describe
biogenesis
current
methods
for
isolation
characterization,
emphasizing
cargo
female
reproductive
processes,
gametogenesis
implantation,
potential
involvement
human
disorders.
Язык: Английский
From Germ Cells to Implantation: The Role of Extracellular Vesicles
Опубликована: Июль 4, 2024
Extracellular
vesicles
represent
a
large
heterogeneous
class
of
near
and
long-distance
intercellular
communication
mediators,
released
by
both
prokaryotic
eukaryotic
cells.
Specifically,
the
scientific
community
has
shown
growing
interest
in
exosomes,
which
are
nano-sized
with
an
endosomal
origin.
Not
so
long
ago,
physiological
goal
exosome
generation
was
largely
unknown
required
more
investigation;
at
first,
it
hypothesized
that
exosomes
able
to
remove
excess,
rejects
unnecessary
constituents
from
cells
preserve
cellular
homeostasis.
However,
thanks
recent
studies,
central
role
regulating
dialogue
emerged.
Exosomes
act
as
vectors
on
cell-cell
signaling
their
cargo,
proteins,
lipids,
nucleic
acids,
influence
pathological
processes.
The
findings
widespread
spectrum
biomedical
applications
diagnosis
prognosis
thera-pies.
In
this
review,
we
describe
biogenesis
current
methods
for
isolation
characterization,
emphasizing
cargo
female
reproductive
processes,
gametogenesis
implantation,
potential
involvement
human
disorders.
Язык: Английский
Mammalian embryo culture media: now and into the future
Reproduction Fertility and Development,
Год журнала:
2023,
Номер
36(2), С. 66 - 80
Опубликована: Окт. 13, 2023
For
over
70
years,
since
the
culture
of
first
mammalian
embryo
in
vitro,
scientists
have
undertaken
studies
to
devise
and
optimise
media
support
manipulation
gametes
embryos.
This
area
research
became
especially
active
late
1970s
onwards
following
successful
birth
human
vitro
fertilised
embryo.
review
summarises
some
key
advances
time
based
on
a
greater
understanding
biochemical
milieu
reproductive
tract.
It
highlights
how
learnings
from
mice
agricultural
species
informed
compositions,
particular
inclusion
albumin,
growth
factors,
cytokines,
antioxidants
into
contemporary
formulations,
these
may
then
turn
help
inform
guide
development
systems
used
other
arenas,
agriculture.
Additionally,
it
will
highlight
introduction
new
technologies,
such
as
timelapse,
can
influence
current
trends
composition
usage
that
see
return
single
step
medium.
Язык: Английский
Biogenesis of Extracellular Vesicles (EVs) and the Potential Use of Embryo-Derived EVs in Medically Assisted Reproduction
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
26(1), С. 42 - 42
Опубликована: Дек. 24, 2024
Extracellular
vesicles
(EVs)
are
lipid
bilayer-bound
particles
released
from
cells
that
cannot
replicate
on
their
own,
play
a
crucial
role
in
intercellular
communication,
and
implicated
various
physiological
pathological
processes.
Within
the
domain
of
embryo
culture
media
research,
extensive
studies
have
been
conducted
to
evaluate
viability
by
analyzing
spent
medium.
Advanced
methodologies
such
as
metabolomic
profiling,
proteomic
genomic
analyses,
transcriptomic
non-coding
RNA
assessments,
oxidative
status
measurements
employed
further
understand
molecular
characteristics
embryos
improve
selection
criteria
for
successful
implantation.
In
field
EVs,
only
limited
number
embryo-conditioned
medium,
indicating
significant
gap
knowledge
regarding
potential
EVs
development
Therefore,
this
review
aims
current
research
findings
enriched
animal
human
By
unraveling
link
between
embryo-derived
clinical
settings,
might
enhance
embryo-selection
methods
assisted
reproductive
technologies,
eventually
increasing
success
rates
fertility
treatments
advancing
our
understanding
mechanisms
underlying
implantation
humans.
Язык: Английский
Micro-RNA (miRNA) epigenetic profiling of plasma small extracellular vesicles (sEV) – sEV miRNA as diagnostic biomarker of fertility
Research Square (Research Square),
Год журнала:
2023,
Номер
unknown
Опубликована: Авг. 3, 2023
Abstract
Fertility
is
determined
to
a
significant
extent
by
its
underlying
genetics
and
success
of
pregnancy
considered
as
tool
define
fertility.
A
substantial
knowledge
gap
exists
however,
regarding
epigenetic
abnormalities
resulting
in
infertility.
The
accuracy
information
concerning
fertility
critical
the
an
infertility
treatment
plan.
Here,
authors
explore
use
value
blood
plasma
small
extracellular
vesicle
(sEV)
derived
micro-RNA
(miRNA)
biomarkers
Next-generation
miRNA
sequencing
identified
14
differentially
expressed
(DE)
miRNAs
with
confidence
between
low
fertile
(LF)
sEV
high
(HF)
(FDR
<
0.05
-logFC
>
2),
isolated
from
dairy
cows
(n
=
10
per
each
HF
LF
group).
Interestingly,
majority
DE
were
uniquely
packaged
into
not
found
circulating
plasma.
Validation
using
qRT-PCR
assays
indicated
similar
expression
patterns
miR-17-5p,
miR-2285dd,
miR-2335,
miR-12054
miR-2285aw,
confirmed
that
miR-181b-5p
was
significantly
upregulated
(P
0.0093,
Fold
change
2.665).
results
this
study
suggest
reflect
overall
status
including
physiological
endometrium.
Moreover,
validated
prognostic
biomarker
Язык: Английский