Biomedicines,
Journal Year:
2024,
Volume and Issue:
12(9), P. 2106 - 2106
Published: Sept. 15, 2024
In
recent
years,
cancer
management
has
benefitted
from
new
effective
treatments,
including
immunotherapy.
While
these
therapies
improve
survival
rates,
they
can
alter
immune
responses
and
cause
long-term
side
effects,
of
which
gonadotoxic
effects
the
potential
impact
on
male
female
fertility
are
growing
concerns.
Immunotherapies,
such
as
checkpoint
inhibitors,
immunomodulators,
monoclonal
antibodies,
CAR-T,
lead
to
elevated
levels
proinflammatory
cytokines
immune-related
adverse
events
that
may
exacerbate
problems.
Immunotherapy-related
inflammation,
characterized
by
cytokine
imbalances
activation
pathways
AMPK/mTOR,
been
implicated
in
mechanisms
impairment.
men,
hypospermatogenesis
aspermatogenesis
have
observed
after
treatment
with
direct
gonads,
particularly
through
inhibition
cytotoxic
T
lymphocyte
antigen-4.
women,
both
damage
ovarian
reserves,
recurrent
pregnancy
loss,
implantation
failure
documented,
secondary
a
complex
interplay
between
cells,
cells
uterine
NK
cells.
this
review,
immunotherapy
patients
hematological
cancers
was
analyzed.
area
is
still
underexplored,
preservation
methods
remain
crucial.
Future
studies
should
investigate
immunotherapy’s
establish
standardized
protocols.
The
outer
surface
of
chorionic
villi
in
the
human
placenta
consists
a
single
multinucleated
cell
called
syncytiotrophoblast
(STB).
unique
cellular
ultrastructure
STB
presents
challenges
deciphering
its
gene
expression
signature
at
single-cell
level,
as
contains
billions
nuclei
cell.
There
are
many
gaps
understanding
molecular
mechanisms
and
developmental
trajectories
involved
formation
differentiation.
To
identify
underlying
control
STB,
we
performed
comparative
nucleus
(SN)
(SC)
RNA
sequencing
on
placental
tissue
tissue-derived
trophoblast
organoids
(TOs).
We
found
that
SN
was
essential
to
capture
population
from
both
TOs.
Differential
pseudotime
analysis
TO-derived
identified
three
distinct
nuclear
subtypes
reminiscent
those
recently
vivo
.
These
included
juvenile
exhibited
CTB
marker
expression,
enriched
genes
oxygen
sensing,
fully
differentiated
subtype.
Notably,
suspension
culture
conditions
TOs
restore
native
orientation
(STB
out
)
showed
elevated
canonical
markers
pregnancy
hormones,
along
with
greater
proportion
terminally
mature
subtype,
compared
cultivated
an
inverted
polarity
).
Gene
regulatory
novel
differentiation
conserved
TOs,
including
chromatin
remodeler
RYBP,
STB-specific
protein
expression.
Finally,
signatures
amongst
first
trimester
tissue,
full-term
identifying
commonalities
but
also
notable
variability
across
each
sample
type.
This
indicates
is
responsive
environmental
context.
Our
findings
emphasize
utility
accurately
model
observed
,
offering
versatile
platform
for
unraveling
governing
functions
biology
disease.
Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 9, 2024
AbstractBackground
Abnormal
interactions
among
decidual
cells,
natural
killer
(dNK)
and
trophoblasts
are
implicated
in
contributing
to
the
placenta
accreta
spectrum
(PAS).
However,
specific
details
of
these
remain
unclear.Methods
Normal
human
placental
maternal
decidua-mesenchymal
stem
cells
(MD-MSCs)
pathological
MD-MSCs
from
PAS
patients
(PAs)
were
isolated
cultured
serum-free
conditions.
Decidualization
was
induced
using
hormonal
cocktails:
estradiol
(E2)/
progesterone
(P4)
chemical
agents
8-br-cAMP/
medroxyprogesterone
acetate
(MPA)
for
both
PAs.
dNK-like
generated
peripheral
(pNK)
through
induction.
Interactions
dNK
studied
a
transwell
co-culture
system.
Bulk
RNA-seq
analysis
performed
identify
differential
genes
between
PAs
explored
their
potential
role
immune
tolerance
regulation
NK
trophoblast
invasion.Results
This
study
aims
explore
correlation
defective
decidualization
endometrial
stromal
dysregulated
cell
proliferation,
leading
excessive
invasion
development
PAS.
defects
confirmed
PAs,
characterized
by
reduced
morphological
changes
altered
expression
levels
biomarkers
at
mRNA
protein
levels,
potentially
associated
with
overexpression
estrogen
receptor
(ER).
Furthermore,
normal
exhibited
similar
patterns
regulating
invasion,
suggesting
an
indirect
impact
impaired
on
behavior.
Interestingly,
decidualized
(De-MD-MSCs)
showed
induce
conversion
pNK
into
which
displayed
cytotoxicity
enhanced
KIR2DL4
expression,
possibly
upregulated
Csf3,
Il1β,
Tgfb1.
Additionally,
increased
proliferation
when
co-cultured
regulated
Cxcl12,
Il33,
Tgfb1,
Vegfa,
Vegfc,
enhancing
spiral
artery
remodeling.
Conditioned
medium
derived
PAs-induced
demonstrated
higher
capacity
promote
dose-dependent
manner.Conclusion
may
contribute
pathogenesis
PAS,
providing
valuable
insights
its
mechanisms
therapeutic
interventions.
Biomedicines,
Journal Year:
2024,
Volume and Issue:
12(9), P. 2106 - 2106
Published: Sept. 15, 2024
In
recent
years,
cancer
management
has
benefitted
from
new
effective
treatments,
including
immunotherapy.
While
these
therapies
improve
survival
rates,
they
can
alter
immune
responses
and
cause
long-term
side
effects,
of
which
gonadotoxic
effects
the
potential
impact
on
male
female
fertility
are
growing
concerns.
Immunotherapies,
such
as
checkpoint
inhibitors,
immunomodulators,
monoclonal
antibodies,
CAR-T,
lead
to
elevated
levels
proinflammatory
cytokines
immune-related
adverse
events
that
may
exacerbate
problems.
Immunotherapy-related
inflammation,
characterized
by
cytokine
imbalances
activation
pathways
AMPK/mTOR,
been
implicated
in
mechanisms
impairment.
men,
hypospermatogenesis
aspermatogenesis
have
observed
after
treatment
with
direct
gonads,
particularly
through
inhibition
cytotoxic
T
lymphocyte
antigen-4.
women,
both
damage
ovarian
reserves,
recurrent
pregnancy
loss,
implantation
failure
documented,
secondary
a
complex
interplay
between
cells,
cells
uterine
NK
cells.
this
review,
immunotherapy
patients
hematological
cancers
was
analyzed.
area
is
still
underexplored,
preservation
methods
remain
crucial.
Future
studies
should
investigate
immunotherapy’s
establish
standardized
protocols.
