PLoS ONE,
Год журнала:
2024,
Номер
19(12), С. e0315750 - e0315750
Опубликована: Дек. 13, 2024
Polycystic
ovary
syndrome
(PCOS)
is
a
prevalent
yet
complex
reproductive
endocrine
disorder
affecting
11–13%
of
women
worldwide.
Its
main
symptoms
include
elevated
androgen
levels,
irregular
menstrual
cycles,
and
long-term
metabolic
offspring
health
implications.
Despite
the
disease’s
multifaceted
nature
involving
genetic,
epigenetic,
environmental
factors,
role
alternative
splicing
in
ovarian
granulosa
cells
remains
relatively
unexplored.
This
study
aims
to
investigate
transcriptional
characteristics
PCOS
patients
elucidate
potential
functional
consequences
these
changes.
Analysis
previous
published
transcriptome
sequencing
data
identified
491
upregulated
401
downregulated
genes
patients,
significantly
involved
immune-related
processes.
Additionally,
1250
differential
events,
predominantly
exon
skipping
947
genes,
were
detected.
These
with
patterns
found
be
enriched
endoplasmic
reticulum
stress
protein
post-translational
modification
processes,
suggesting
their
pathology.
Moreover,
highlighted
that
utilization
different
splice
isoforms
YAP1
gene
may
impact
its
interaction
Hippo
signaling
pathway,
influencing
pathogenesis
PCOS.
findings
underscore
substantial
alterations
providing
novel
viewpoint
for
comprehending
molecular
underpinnings
avenues
therapeutic
intervention.
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 21, 2024
Abstract
IRE1α,
a
type
I
transmembrane
protein
characterized
by
cytoplasmic
serine/threonine
kinase
domain,
is
related
to
ER
stress
and
function
maintenance.
In
this
study,
4µ8c,
highly
effective
selective
inhibitor
of
IRE1α
RNase,
APY29,
an
ATP
competitive
inhibitor,
inhibiting
autophosphorylation
the
were
employed
elucidate
on
proliferation
ovarian
granulosa
cells,
with
ultimate
goal
identifying
novel
strategies
methodologies
for
prevention
treatment
associated
diseases.
Human
cells
(SVOG)
cultured
in
vitro
treated
inhibitors
4µ8c
APY29.
It
was
shown
that
inhibition
reduced
cell
ability
dealing
misfolded
protein,
triggered
oxidative
stress,
altered
mitochondrial
membrane
potential,
inflicted
DNA
damage,
eventually
lead
apoptosis.
PLoS ONE,
Год журнала:
2024,
Номер
19(12), С. e0315750 - e0315750
Опубликована: Дек. 13, 2024
Polycystic
ovary
syndrome
(PCOS)
is
a
prevalent
yet
complex
reproductive
endocrine
disorder
affecting
11–13%
of
women
worldwide.
Its
main
symptoms
include
elevated
androgen
levels,
irregular
menstrual
cycles,
and
long-term
metabolic
offspring
health
implications.
Despite
the
disease’s
multifaceted
nature
involving
genetic,
epigenetic,
environmental
factors,
role
alternative
splicing
in
ovarian
granulosa
cells
remains
relatively
unexplored.
This
study
aims
to
investigate
transcriptional
characteristics
PCOS
patients
elucidate
potential
functional
consequences
these
changes.
Analysis
previous
published
transcriptome
sequencing
data
identified
491
upregulated
401
downregulated
genes
patients,
significantly
involved
immune-related
processes.
Additionally,
1250
differential
events,
predominantly
exon
skipping
947
genes,
were
detected.
These
with
patterns
found
be
enriched
endoplasmic
reticulum
stress
protein
post-translational
modification
processes,
suggesting
their
pathology.
Moreover,
highlighted
that
utilization
different
splice
isoforms
YAP1
gene
may
impact
its
interaction
Hippo
signaling
pathway,
influencing
pathogenesis
PCOS.
findings
underscore
substantial
alterations
providing
novel
viewpoint
for
comprehending
molecular
underpinnings
avenues
therapeutic
intervention.