Epithelial to Mesenchymal Transition in the Endometrium Mediated by HOXA10 drives Embryo Implantation
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 10, 2025
Abstract
Embryo
implantation
requires
the
breaching
of
endometrial
luminal
epithelium
(LE)
to
facilitate
invasion.
In
this
study,
we
report
that
during
implantation,
LE
cells
undergo
partial
epithelial-to-mesenchymal
transition
(pEMT)
specifically
at
sites.
This
pEMT
in
is
critical,
as
vivo
knockdown
EMT
transcription
factor
Twist
2
inhibits
embryo
implantation.
Furthermore,
observed
a
reduction
expression
HOXA10
Interestingly,
HOXA10-hypomorphic
mice
and
human
epithelial
(RL95-2)
with
(
KD)
also
acquire
migratory
phenotype
vitro
,
suggesting
loss
drives
epithelium.
The
KD
have
higher
score
differential
genes
associated
cell
migration
TGF-β
signaling
pathways.
We
determined
genome-wide
occupancy
sites
identified
1,246
direct
targets
had
significant
roles
EMT.
Collectively,
our
findings
suggest
required
maintain
an
state
its
activates
mesenchymal
resulting
phenotype.
adds
member
MET
inducer
team
engage
mutually
inhibitory
feedback
loops
directly
or
indirectly
team.
summary,
study
establishes
critical
step
for
reveals
regulates
process.
Язык: Английский
Systematic review on the DNA methylation role in endometriosis: current evidence and perspectives
Clinical Epigenetics,
Год журнала:
2025,
Номер
17(1)
Опубликована: Фев. 21, 2025
Endometriosis
appears
to
have
a
multilayered
etiology,
with
genetic
and
epigenetic
factors
each
contributing
half
of
the
pathogenesis.
The
molecular
processes
that
underlie
onset
endometriosis
are
yet
unclear,
but
it
is
assumed
an
important
contributor
in
etiopathology
disease
DNA
methylation.
We
conducted
systematic
review
literature
regarding
methylation
following
PRISMA
guidelines.
Records
were
obtained
from
PubMed
Web
Science
on
May
31,
2024.
Original
research
articles
analyzing
regional
or
genome-wide
patients
confirmed
(by
surgery
and/or
histological
examination)
given
consideration
for
inclusion.
Only
human
studies
included,
there
no
restrictions
types
tissue
was
analyzed
(i.e.,
endometrium,
blood,
fetal
tissue).
study
selection
process
run
by
two
manual
reviewers.
In
parallel,
adapted
virtual
artificial
intelligence-powered
reviewer
operated
results
compared
reviewers'
selection.
Studies
divided
into
targeted
(e.g.,
single
gene
region
level)
epigenome-wide
association
studies.
For
each,
we
extracted
list
genes
studied
precise
location
CpGs
status
according
groups
compared.
Quality
assessment
performed
Newcastle–Ottawa
scale.
evidence
graded
Grading
Recommendations
Assessment,
Development
Evaluation.
A
total
955
screened,
70
identified
as
relevant
review.
Our
analyses
displayed
could
be
polyepigenetic
alterations
specific
implicated
major
signaling
pathways
(cell
proliferation,
differentiation,
division
[PI3K-Akt
Wnt-signaling
pathway],
cell
[MAPK
adhesion,
communication,
developmental
processes,
response
hormone,
apoptosis,
immunity,
neurogenesis,
cancer).
indicates
associated
modifications
at
involved
key
endometrial
biological
particularly
ectopic
endometrium.
As
integral
component
pathogenesis
endometriosis,
identification
biomarkers
would
likely
help
better
understand
its
causes
aggravating
well
potentially
facilitate
diagnosis
support
development
new
therapeutic
approaches.
observed
both
eutopic
endometrium
healthy
their
localization
may
influence
female
reproductive
system.
DMP:
Differentially
methylated
position.
DMR:
region.
Язык: Английский
The distribution of four homeobox proteins in the bovine stomach compartments during the fetal period
Revista Científica de la Facultad de Ciencias Veterinarias,
Год журнала:
2025,
Номер
35(2), С. 11 - 11
Опубликована: Апрель 4, 2025
Homeobox
proteins
undertake
important
roles
in
the
determination
of
cell
identity
during
embryonic
development,
differentiation
stem
cells,
morphogenesis,
and
formation
development
mammalian
gastrointestinal
tract.
Based
on
these
data,
this
study
was
designed
to
determine
immunohistochemical
localization
expression
levels
HOXA10,
HOXA11,
HOXC6
HOXB6,
which
are
subunits
homeobox
proteins,
rumen,
reticulum,
omasum
abomasum
fetal
development.
For
purpose,
fetuses
obtained
from
private
slaughterhouses
were
grouped
according
their
crown-rump
length
(CRL)
measurements,
gestational
trimester
they
belonged
to,
as
follows:
first
(69-89
days
old/10
fetuses),
second
(99-178
fetuses)
third
(188-269
fetuses).
Gastric
tissue
samples
taken
each
group
underwent
routine
histological
processing
staining.
Immunohistochemical
staining
demonstrated
that
HOXA11
expressed
at
varying
abomasum,
stronger
epithelial
smooth
muscle
cells.
On
other
hand,
while
there
almost
no
HOXB6
cells
rumen
trimesters
gestation,
remaining
gastric
components
immunonegative.
findings,
it
concluded
some
could
have
critical
morphogenesis
histogenesis
bovine
compartments,
thus,
contribute
lifetime
performance
productivity
cattle
terms
milk
meat
yields.
Язык: Английский
Revolutionizing Stem Cell Therapy: A Comparative Analysis of Diverse Mesenchymal Stem Cells for Enhanced Endometrial Regeneration
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 17, 2025
Abstract
Background:
Endometrial
injury,
particularly
intrauterine
adhesions
(Asherman’s
syndrome),
represents
a
prevalent
condition
that
significantly
compromises
female
fertility.
Current
clinical
interventions
predominantly
involve
hysteroscopic
surgery,
followed
by
the
placement
of
barriers
and
administration
oral
estrogen
to
facilitate
endometrial
regeneration.
Nevertheless,
in
patients
with
severe
adhesions,
postoperative
pregnancy
rates
remain
low,
ranging
from
22.2%
33.3%.
Mesenchymal
stem
cells
(MSCs),
owing
their
multilineage
differentiation
potential
tissue
repair
capabilities,
have
emerged
as
promising
candidates
for
treatment
regenerative
disorders.
This
study
aimed
compare
efficacy
MSCs
derived
bone
marrow,
umbilical
cord,
adipose
tissue,
decidua
damaged
endometrium.
Methods:
The
proliferation
capabilities
decidual
MSCs,
cord
marrow
adipose-derived
at
passages
1,
3,
5
were
evaluated
using
CCK8
assay.
In
vitro,
cytokine-induced
was
employed
stimulate
expression
epithelial
cell
surface
markers
assessed
through
immunofluorescence
Western
blot
analyses
into
cells.
vivo,
an
adhesion
rat
model
received
MSC
infusions,
restoration
morphology
subsequently
examined
compared
across
different
groups.
Results:
Bone
demonstrated
highest
rate,
while
exhibited
lowest.
Notably,
displayed
enhanced
capacity
differentiate
other
sources.
Furthermore,
adhesion,
resulted
most
pronounced
improvement
repair.
Conclusions:
Decidual
demonstrate
superior
vitro
exhibit
effective
vivo
potentially
mediated
secretion
various
cytokines
immunomodulatory
mechanisms.
provides
critical
theoretical
experimental
evidence
supporting
application
Despite
certain
limitations,
such
absence
validation,
present
novel
therapeutic
strategy
conditions
related
injury.
Future
trials
mechanistic
studies
are
necessary
further
validate
potential.
Язык: Английский
A Dual-Interaction Supramolecular Hydrogel System for siRNA Delivery to Enhance Endometrial Receptivity in Stem Cell Therapy
Biomacromolecules,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 25, 2025
Endometrial
receptivity
is
crucial
for
embryo
implantation
success.
Stem
cell
therapy
shows
promise
improving
endometrial
health.
We
developed
a
supramolecular
hydrogel
scaffold
based
on
stereocomplexed
triblock
copolymers
(MPEG-(sc-PLA)-PEI)
and
α-cyclodextrin
codelivering
menstrual
blood-derived
stem
cells
(MenSCs)
siRNA
targeting
DNA
methyl
transferase
1
(DNMT1),
enabling
RNAi-mediated
gene
silencing
to
improve
receptivity.
The
resulting
α-CD/MPEG-(sc-PLA)-PEI
hydrogels
exhibited
high
mechanical
stability,
excellent
self-healing
capabilities,
sustained
release
via
dual-interaction
mechanism
involving
host-guest
interaction
stereocomplexation.
In
vitro
studies
indicated
superior
cellular
uptake
of
DNMT1
encapsulated
within
MPEG-(sc-PLA)-PEI
complexes,
in
significant
upregulation
markers,
including
HOXA10,
ITGB3,
E-cadherin.
vivo
experiments
showed
that
siRNA-loaded
facilitated
remodeling
through
therapeutic
transgene
expression
MenSCs.
These
findings
suggest
this
multifunctional
system
may
serve
as
an
effective
tool
cell-based
therapies
aimed
at
enhancing
Язык: Английский