Redox-Driven Epigenetic Modifications in Sperm: Unraveling Paternal Influences on Embryo Development and Transgenerational Health
Antioxidants,
Год журнала:
2025,
Номер
14(5), С. 570 - 570
Опубликована: Май 9, 2025
Male-factor
infertility
accounts
for
nearly
half
of
all
cases,
and
mounting
evidence
points
to
oxidative
stress
as
a
pivotal
driver
sperm
dysfunction,
genetic
instability,
epigenetic
dysregulation.
In
particular,
the
DNA
lesion
8-hydroxy-2′-deoxyguanosine
(8-OHdG)
has
emerged
central
mediator
at
interface
damage
regulation.
We
discuss
how
this
can
disrupt
key
mechanisms
such
methylation,
histone
modifications,
small
non-coding
RNAs,
thereby
influencing
fertilization
outcomes,
embryo
development,
offspring
health.
propose
that
interplay
between
reprogramming
is
further
exacerbated
by
aging
in
both
paternal
maternal
germlines,
creating
“perfect
storm”
increases
risk
heritable
(epi)mutations.
The
consequences
unresolved
lesions
thus
persist
beyond
fertilization,
contributing
transgenerational
health
risks.
Finally,
we
explore
promise
potential
pitfalls
antioxidant
therapy
strategy
mitigate
damage.
While
supplementation
may
hold
significant
therapeutic
value
men
with
subfertility
experiencing
elevated
stress,
careful,
personalized
approach
essential
avoid
reductive
unintended
disruptions.
Recognizing
dual
role
shaping
genome
epigenome
underscores
need
integrating
redox
biology
into
reproductive
medicine,
aim
improving
fertility
treatments
safeguarding
future
generations.
Язык: Английский
Inter- and transgenerational heritability of preconception chronic stress or alcohol exposure: Translational outcomes in brain and behavior
Neurobiology of Stress,
Год журнала:
2023,
Номер
29, С. 100603 - 100603
Опубликована: Дек. 25, 2023
Chronic
stress
and
alcohol
(ethanol)
use
are
highly
interrelated
can
change
an
individual's
behavior
through
molecular
adaptations
that
do
not
the
DNA
sequence,
but
instead
gene
expression.
A
recent
wealth
of
research
has
found
these
nongenomic
changes
be
transmitted
across
generations,
which
could
partially
account
for
"missing
heritability"
observed
in
genome-wide
association
studies
disorder
other
stress-related
neuropsychiatric
disorders.
In
this
review,
we
summarize
behavioral
outcomes
inheritance
chronic
ethanol
exposure
germline
mechanisms
give
rise
to
heritability.
doing
so,
outline
need
further
to:
(1)
Investigate
individual
paternal,
maternal,
biparental
stress-
ethanol-related
inheritance;
(2)
Synthesize
dissect
cross-generational
exposure;
(3)
Determine
preconception
contribute
alcohol-related
disease
risk,
using
cancer
as
example.
detailed
understanding
effects
and/or
will
yield
novel
insight
into
impact
ancestral
perturbations
on
risk
generations
uncover
actionable
targets
improve
human
health.
Язык: Английский
Parental Alcohol Exposures Associate with Lasting Mitochondrial Dysfunction and Accelerated Aging in a Mouse Model
Aging and Disease,
Год журнала:
2024,
Номер
unknown, С. 0 - 0
Опубликована: Янв. 1, 2024
Although
detrimental
changes
in
mitochondrial
morphology
and
function
are
widely
described
symptoms
of
fetal
alcohol
exposure,
no
studies
have
followed
these
deficits
into
adult
life
or
determined
if
they
predispose
individuals
with
spectrum
disorders
(FASDs)
to
accelerated
biological
aging.
Here,
we
used
a
multiplex
preclinical
mouse
model
compare
markers
cellular
senescence
age-related
outcomes
induced
by
maternal,
paternal,
dual-parental
exposures.
We
find
that
even
middle
(postnatal
day
300),
the
offspring
alcohol-exposed
parents
exhibited
significant
increases
stress-induced
premature
brain
liver,
including
an
upregulation
cell
cycle
inhibitory
proteins
increased
senescence-associated
β-galactosidase
activity.
Strikingly,
male
offspring,
observe
interaction
between
maternal
paternal
use,
histological
indicators
liver
disease
exceeding
those
either
use
alone.
Our
indicate
chronic
parental
causes
enduring
dysfunction
resulting
reduced
NAD+/NAHD
ratio
altered
expression
NAD+-dependent
deacetylases
SIRT1
SIRT3.
These
observations
suggest
some
aspects
FASDs
may
be
linked
aging
due
programmed
regulation
bioenergetics.
Язык: Английский
Chronic paternal alcohol exposures induce dose-dependent changes in offspring craniofacial shape and symmetry
Frontiers in Cell and Developmental Biology,
Год журнала:
2024,
Номер
12
Опубликована: Июль 1, 2024
Although
dose-response
analyses
are
a
fundamental
tool
in
developmental
toxicology,
few
studies
have
examined
the
impacts
of
toxicant
dose
on
non-genetic
paternal
inheritance
offspring
disease
and
dysgenesis.
In
this
study,
we
used
geometric
morphometric
to
examine
different
levels
preconception
alcohol
exposure
craniofacial
shape
symmetry
mouse
model.
Procrustes
ANOVA
followed
by
canonical
variant
analysis
facial
relationships
revealed
that
Low-,
Medium-,
High-dose
treatments
each
induced
distinct
changes
symmetry.
Our
identified
threshold
between
1.543
2.321
g/kg/day.
Below
threshold,
shape,
including
right
shift
features.
contrast,
above
exposures
caused
shifts
both
center,
disrupting
Consistent
with
previous
clinical
studies,
predominantly
mapped
regions
lower
portion
face,
mandible
(lower
jaw)
maxilla
(upper
jaw).
Notably,
high-dose
also
impacted
positioning
eye.
reveal
use
may
be
an
unrecognized
factor
contributing
incidence
severity
alcohol-related
defects,
complicating
diagnostics
fetal
spectrum
disorders.
Язык: Английский