The Journal of Physiology,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 5, 2025
Abstract
Fetal
chronic
hypoxia
is
a
common
pregnancy
complication
associated
with
fetal
growth
restriction.
Growth‐restricted
offspring
have
higher
risk
for
liver
metabolic
disease.
Our
objective
was
to
better
understand
how
impacts
the
developing
liver.
We
hypothesized
that
promotes
hepatocellular
injury,
shifts
nutrient
metabolism,
and
activates
energetic
oxidative
stress
in
used
an
ovine
model
of
where
pregnant
ewes
were
housed
under
normoxic
(CON)
or
hypoxic
(HOX)
conditions
30
days
late
gestation.
obtained,
histologically
analysed
profiled
using
bulk‐RNA
sequencing
metabolomics.
Nutrient
signalling
pathways
also
measured.
HOX
fetuses
had
greater
hepatic
periportal
collagen
deposition.
Metabolomics
transcriptomics
predicted
disruptions
central
carbon
mitochondrial
dysfunction
decreased
phosphorylation.
In
support,
we
found
potentiation
gluconeogenic
pathway
increased
lactate
production,
pyruvate
oxidation
AMPK
activation.
By
contrast
effects,
livers
maintained
antioxidant
capacity.
Interestingly,
acylcarnitines
increased,
yet
triglyceride
content
similar.
Although
there
little
activation
markers,
such
as
lipid
peroxidation
oxidized
glutathione,
uncovered
unique
profile
stress‐related
metabolites
association
collagen.
Thus,
deposition,
indicating
adaptations
metabolism.
These
results
provide
new
insight
into
may
initiate
fibrotic
disease
adverse
pregnancy.
image
Key
points
Chronic
exposure
injury.
Hypoxic
This
provides
hypoxia,
restriction,
risk.
Antioxidants,
Год журнала:
2022,
Номер
11(3), С. 511 - 511
Опубликована: Март 7, 2022
Hypertension
remains
the
leading
cause
of
disease
burden
worldwide.
can
originate
in
early
stages
life.
A
growing
body
evidence
suggests
that
oxidative
stress,
which
is
characterized
as
a
reactive
oxygen
species
(ROS)/nitric
oxide
(NO)
disequilibrium,
has
pivotal
role
hypertension
developmental
origins.
Results
from
animal
studies
support
idea
early-life
stress
causes
programming
prime
blood
pressure
(BP)-controlled
organs
such
brain,
kidneys,
heart,
and
vessels,
to
adult
offspring.
Conversely,
perinatal
use
antioxidants
counteract
therefore
lower
BP.
This
review
discusses
interaction
between
hypertension.
It
will
also
discuss
models,
how
connects
with
other
core
mechanisms,
potential
antioxidant
therapy
novel
preventive
strategy
prevent
Frontiers in Physiology,
Год журнала:
2025,
Номер
15
Опубликована: Янв. 15, 2025
Chronic
fetal
hypoxia
is
commonly
associated
with
growth
restriction
and
can
predispose
to
respiratory
disease
at
birth
in
later
life.
Antenatal
antioxidant
treatment
has
been
investigated
overcome
the
effects
of
oxidative
stress
utero
improve
outcomes.
We
aimed
determine
if
chronic
antenatal
administration
persist
lung
early
adulthood.
Chronically
catheterised
pregnant
sheep
were
exposed
normoxia
(N;
n
=
20)
or
(H;
18;
10%
O2)
±
maternal
daily
i.
v.
saline
(N
11;
H
8)
Vitamin
C
(VC;
NVC
9;
HVC
10)
from
105
138
days
(term,
∼145
days).
Lungs
collected
female
lambs
9
months
after
(early
adulthood).
Lung
tissue
expression
genes
proteins
regulating
stress,
mitochondrial
function,
signalling,
glucocorticoid
surfactant
maturation,
inflammation
airway
remodelling
measured.
upregulated
markers
prooxidant,
lipid
transport
pathways
normalized
prooxidant
markers,
increased
endogenous
antioxidant,
vasodilator
inflammatory
altered
regulation
signalling
availability.
There
are
differential
on
molecular
lungs
normoxic
hypoxic
pregnancy
The Journal of Physiology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 27, 2025
Abstract
The
mechanisms
that
drive
placental
dysfunction
in
pregnancies
complicated
by
hypoxia
and
fetal
growth
restriction
remain
poorly
understood.
Changes
to
mitochondrial
respiration
contribute
cellular
conditions
of
have
been
implicated
the
pathoaetiology
pregnancy
complications,
such
as
pre‐eclampsia.
We
used
bespoke
isobaric
hypoxic
chambers
a
combination
functional,
molecular
imaging
techniques
study
metabolism
dynamics
sheep
undergoing
pregnancy.
show
triggers
shift
capacity
away
from
β‐oxidation
complex
I‐mediated
respiration,
while
maintaining
total
oxidative
phosphorylation
capacity.
There
are
also
complex‐specific
changes
electron
transport
chain
composition
switch
towards
fission.
Hypoxic
placentas
increased
activation
non‐canonical
unfolded
protein
response
pathway
enhanced
insulin
like
factor
2
signalling.
Combined,
therefore,
data
placenta
undergoes
significant
metabolic
morphological
adaptations
maintain
energy
balance.
Chronic
during
activated
stress
pathways,
leading
alterations
dynamics,
seen
women
with
image
Key
points
Hypoxia
shifts
I.
Complex‐specific
occur
composition.
Activation
is
heightened
placentas.
Enhanced
signalling
observed
undergo
functional
for
European Heart Journal,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 7, 2024
Pregnancy
complicated
by
maternal
obesity
contributes
to
an
increased
cardiovascular
risk
in
offspring,
which
is
increasingly
concerning
as
the
rates
of
and
disease
are
higher
than
ever
before
still
growing.
There
has
been
much
research
humans
preclinical
animal
models
understand
impact
on
offspring
health.
This
review
summarizes
what
known
about
phenotype,
describing
a
mechanistic
role
for
oxidative
stress,
metabolic
inflexibility,
mitochondrial
dysfunction
mediating
these
impairments.
It
also
discusses
secondary
postnatal
insults,
may
reveal
latent
deficits
that
originated
utero.
Finally,
current
interventional
efforts
gaps
knowledge
limit
developmental
origins
obese
pregnancy
highlighted.
Biomedicines,
Год журнала:
2025,
Номер
13(2), С. 452 - 452
Опубликована: Фев. 12, 2025
Cardiovascular-kidney-metabolic
syndrome
(CKMS)
has
become
a
significant
global
health
challenge.
Since
CKMS
often
originates
early
in
life,
as
outlined
by
the
developmental
origins
of
and
disease
(DOHaD)
concept,
prevention
is
more
effective
strategy
than
treatment.
Various
animal
models,
classified
environmental
exposures
or
mechanisms,
are
used
to
explore
CKMS.
However,
no
single
model
can
fully
replicate
all
aspects
its
clinical
stages,
limiting
advancement
preventive
therapeutic
strategies.
This
review
aims
assist
researchers
comparing
strengths
limitations
common
models
programming
studies
highlighting
key
considerations
for
selecting
suitable
models.
The Journal of Physiology,
Год журнала:
2019,
Номер
597(22), С. 5349 - 5364
Опубликована: Авг. 22, 2019
Key
points
Obstructive
sleep
apnoea
(OSA)
is
characterized
by
intermittent
hypoxia,
which
causes
oxidative
stress
and
inflammation
increases
the
risk
of
cardiovascular
disease.
OSA
during
pregnancy
adverse
maternal
fetal
outcomes.
The
effects
pre‐existing
in
pregnant
women
on
cardiometabolic
outcomes
offspring
are
unknown.
We
evaluated
basic
metabolic
parameters,
as
well
aortic
vascular
perivascular
adipose
tissue
(PVAT)
function
response
to
adiponectin,
examined
DNA
methylation
adiponectin
gene
promoter
PVAT
16‐week‐old
adult
exposed
gestational
hypoxia
(GIH).
GIH
decreased
body
weights
at
week
1
both
male
female
offspring,
caused
subsequent
weight
food
consumption
only.
Adult
had
normal
levels
lipids,
glucose
insulin,
with
no
endothelial
dysfunction.
exhibited
dyslipidaemia,
insulin
resistance
hyperleptinaemia.
Decreased
endothelial‐dependent
vasodilatation,
loss
anti‐contractile
activity
low
circulating
levels,
increased
pro‐inflammatory
expression
promoter,
occurred
offspring.
Our
results
suggest
that
could
be
developing
disease
adulthood.
Abstract
Perturbations
can
program
develop
diseases
later
life.
a
chronic
condition
frequently
affects
pregnancies
leads
assessed
mice
experiencing
(GIH),
hallmark
OSA,
for
changes
profiles,
nitric
oxide
(NO)‐dependent
relaxations,
activities
responses
tissue.
Pregnant
mouse
dams
were
hypoxic
cycles
(
21–12%)
18
days.
resulted
lower
pups
1,
followed
significant
gain
16
age
but
not
Plasma
leptin
higher
Endothelium‐dependent
relaxation
ACh
abdominal
aorta
was
reduced
Incubation
arteries
from
restored
PVAT.
Both
homogenate
PVAT,
along
an
inflammatory
cytokines.
Pyrosequencing
showed
indicate
through
dysfunction,
associated
epigenetic
modifications
promoter.
Biomedicines,
Год журнала:
2021,
Номер
9(6), С. 623 - 623
Опубликована: Май 31, 2021
Increasing
evidence
suggests
that
fetal
programming
through
environmental
exposure
during
a
critical
window
of
early
life
leads
to
long-term
detrimental
outcomes,
by
so-called
developmental
origins
health
and
disease
(DOHaD).
Hypertension
can
originate
in
life.
Animal
models
are
essential
for
providing
convincing
causal
relationship
between
diverse
early-life
insults
the
hypertension
later
These
include
nutritional
imbalances,
maternal
illnesses,
chemicals,
medication
use.
In
addition
reviewing
various
contribute
origins,
this
review
focuses
on
benefits
animal
addressing
underlying
mechanisms
which
interventions
reprogram
processes
prevent
development
hypertension.
Our
understanding
has
been
enhanced
each
these
models,
narrowing
knowledge
gap
future
clinical
translation.
Circulation,
Год журнала:
2021,
Номер
144(17), С. 1429 - 1443
Опубликована: Окт. 25, 2021
Heart
disease
remains
one
of
the
greatest
killers.
In
addition
to
genetics
and
traditional
lifestyle
risk
factors,
we
now
understand
that
adverse
conditions
during
pregnancy
can
also
increase
susceptibility
cardiovascular
in
offspring.
Therefore,
mechanisms
by
which
this
occurs
possible
preventative
therapies
are
significant
contemporary
interest
community.
A
common
suboptimal
condition
is
a
sustained
reduction
fetal
oxygenation.
Chronic
hypoxia
results
from
any
with
increased
placental
vascular
resistance,
such
as
preeclampsia,
infection,
or
maternal
obesity.
may
arise
at
high
altitude
because
respiratory
disease.
This
article
reviews
short-
long-term
effects
on
system,
importance
chronic
triggering
developmental
origin
future
heart
adult
progeny.
The
work
summarizes
evidence
derived
human
studies
well
rodent,
avian,
ovine
models.
There
focus
discovery
molecular
link
between
prenatal
hypoxia,
oxidative
stress,
Discussion
mitochondria-targeted
antioxidant
therapy
offers
potential
targets
for
clinical
intervention
complicated
hypoxia.
BioMed Research International,
Год журнала:
2022,
Номер
2022, С. 1 - 13
Опубликована: Янв. 13, 2022
Objectives.
Hypertension
(HTN)
is
one
of
the
most
important
risk
factors
for
cardiovascular
diseases.
Despite
advances
in
treatment
and
control
HTN,
prevalence
HTN
still
increasing.
MitoQ
a
supplement
that
acts
on
mitochondria
attenuates
reactive
oxygen
species
(ROS),
which
plays
an
role
health.
miRNAs
play
pathophysiology
HTN.
We
evaluated
effects
supplementation
endurance
training
(ET),
alone
combination,
functional
indices
heart
serum
levels
miR-126,
miR-27a,
antioxidants,
NO,
patients
with
Methods.
In
double-blind
randomized
clinical
trial,
52
male
participants
(age
40-55
years)
were
randomly
divided
into
four
groups
(
)
placebo,
(20
mg/day,
oral),
ET
(cycle
ergometer,
moderate
intensity,
40-60%
VO2
peak,
rate
120-140
b/min,
45
min
day,
three
days/week
six
weeks),
MitoQ+ET.
Cardiac
function
assessed
by
echocardiography
before
after
interventions.
Results.
Systolic
blood
pressure
(SBP)
significantly
decreased
all
intervention
id="M2">
P<0.001
while
DBP
id="M3">
0.01
LV
hypertrophy
id="M4">
0.05
only
MitoQ+ET
group.
Serum
SOD,
GPx,
NO
level
miR-126
increased
groups,
miR-27a
reduced
id="M5">
id="M6">
groups.
Conclusions.
Compared
to
alone,
their
combination
has
more
prominent
improving
cardiac
health
amelioration
BP
These
are
through
modulation
ameliorating
mitochondrial
ROS
production.