Environment International,
Год журнала:
2021,
Номер
155, С. 106693 - 106693
Опубликована: Июнь 10, 2021
Preconception
environmental
conditions
have
been
demonstrated
to
shape
sperm
epigenetics
and
subsequently
offspring
health
development.
Our
previous
findings
in
humans
showed
that
urinary
anti-androgenic
phthalate
metabolites
males
were
associated
with
altered
methylation
blastocyst-stage
embryo
To
corroborate
this,
we
examined
the
effect
of
preconception
exposure
di(2-ethylhexyl)
(DEHP)
on
genome-wide
DNA
gene
expression
profiles
mice.
Eight-week
old
C57BL/6J
male
mice
exposed
either
a
vehicle
control,
low,
or
high
dose
DEHP
(2.5
25
mg/kg/weight,
respectively)
for
67
days
(~2
spermatogenic
cycles)
mated
unexposed
females.
Reduced
representation
bisulfite
sequencing
(RRBS)
epididymal
was
performed
gastrulation
stage
embryos
collected
RRBS
transcriptome
analyses
both
embryonic
extra-embryonic
lineages.
Male
resulted
704
differentially
methylated
regions
(DMRs;
q-value
<
0.05;
≥10%
change)
sperm,
1,716
DMRs
embryonic,
3,181
tissue.
Of
these,
29
overlapped
between
F1
tissues,
half
which
concordant
changes
F0
generations.
transcriptomes
at
E7.5
also
by
including
developmental
families
such
as
Hox,
Gata,
Sox.
Additionally,
ontology
expressed
genes
enrichment
multiple
processes
development,
pattern
specification
morphogenesis.
These
data
indicate
spermatogenesis
adult
may
represent
sensitive
window
alters
methylome
well
developing
embryo.
Cancer Discovery,
Год журнала:
2022,
Номер
12(1), С. 31 - 46
Опубликована: Янв. 1, 2022
The
hallmarks
of
cancer
conceptualization
is
a
heuristic
tool
for
distilling
the
vast
complexity
phenotypes
and
genotypes
into
provisional
set
underlying
principles.
As
knowledge
mechanisms
has
progressed,
other
facets
disease
have
emerged
as
potential
refinements.
Herein,
prospect
raised
that
phenotypic
plasticity
disrupted
differentiation
discrete
hallmark
capability,
nonmutational
epigenetic
reprogramming
polymorphic
microbiomes
both
constitute
distinctive
enabling
characteristics
facilitate
acquisition
capabilities.
Additionally,
senescent
cells,
varying
origins,
may
be
added
to
roster
functionally
important
cell
types
in
tumor
microenvironment.
SIGNIFICANCE:
Cancer
daunting
breadth
scope
its
diversity,
spanning
genetics,
tissue
biology,
pathology,
response
therapy.
Ever
more
powerful
experimental
computational
tools
technologies
are
providing
an
avalanche
"big
data"
about
myriad
manifestations
diseases
encompasses.
integrative
concept
embodied
helping
distill
this
increasingly
logical
science,
new
dimensions
presented
perspective
add
value
endeavor,
fully
understand
development
malignant
progression,
apply
medicine.
Endocrine Reviews,
Год журнала:
2022,
Номер
43(6), С. 927 - 965
Опубликована: Янв. 13, 2022
Polycystic
ovary
syndrome
(PCOS)
is
among
the
most
common
disorders
in
women
of
reproductive
age,
affecting
up
to
15%
worldwide,
depending
on
diagnostic
criteria.
PCOS
characterized
by
a
constellation
interrelated
abnormalities,
including
disordered
gonadotropin
secretion,
increased
androgen
production,
chronic
anovulation,
and
polycystic
ovarian
morphology.
It
frequently
associated
with
insulin
resistance
obesity.
These
metabolic
derangements
cause
major
morbidities
across
lifespan,
anovulatory
infertility
type
2
diabetes
(T2D).
Despite
decades
investigative
effort,
etiology
remains
unknown.
Familial
clustering
cases
has
indicated
genetic
contribution
PCOS.
There
are
rare
Mendelian
forms
extreme
phenotypes,
but
typically
follows
non-Mendelian
pattern
inheritance
consistent
complex
architecture,
analogous
T2D
obesity,
that
reflects
interaction
susceptibility
genes
environmental
factors.
Genomic
studies
have
provided
important
insights
into
disease
pathways
current
criteria
do
not
capture
underlying
differences
biology
different
We
provide
state-of-the-science
review
analyses
PCOS,
an
overview
genomic
methodologies
aimed
at
general
audience
non-geneticists
clinicians.
Applications
will
be
discussed,
strengths
limitations
each
study.
The
contributions
factors,
developmental
origins,
reviewed.
Insights
pathogenesis
architecture
summarized.
Future
directions
for
outlined.
Cell Metabolism,
Год журнала:
2021,
Номер
33(3), С. 513 - 530.e8
Опубликована: Фев. 6, 2021
Polycystic
ovary
syndrome
(PCOS)
is
the
most
common
reproductive
and
metabolic
disorder
affecting
women
of
age.
PCOS
has
a
strong
heritable
component,
but
its
pathogenesis
been
unclear.
Here,
we
performed
RNA
sequencing
genome-wide
DNA
methylation
profiling
ovarian
tissue
from
control
third-generation
PCOS-like
mice.
We
found
that
hypomethylation
regulates
key
genes
associated
with
several
differentially
methylated
are
also
altered
in
blood
samples
compared
healthy
controls.
Based
on
this
insight,
treated
mouse
model
methyl
group
donor
S-adenosylmethionine
it
corrected
their
transcriptomic,
neuroendocrine,
defects.
These
findings
show
transmission
traits
to
future
generations
occurs
via
an
landscape
propose
methylome
markers
as
possible
diagnostic
landmark
for
condition,
while
identifying
potential
candidates
epigenetic-based
therapy.
Protein & Cell,
Год журнала:
2020,
Номер
12(1), С. 7 - 28
Опубликована: Июль 15, 2020
Mammalian
fertilization
begins
with
the
fusion
of
two
specialized
gametes,
followed
by
major
epigenetic
remodeling
leading
to
formation
a
totipotent
embryo.
During
development
pre-implantation
embryo,
precise
reprogramming
progress
is
prerequisite
for
avoiding
developmental
defects
or
embryonic
lethality,
but
underlying
molecular
mechanisms
remain
elusive.
For
past
few
years,
unprecedented
breakthroughs
have
been
made
in
mapping
regulatory
network
dynamic
epigenomes
during
mammalian
early
embryo
development,
taking
advantage
multiple
advances
and
innovations
low-input
genome-wide
chromatin
analysis
technologies.
The
aim
this
review
highlight
most
recent
understanding
embryogenesis
mammals,
including
DNA
methylation,
histone
modifications,
accessibility
3D
organization.
Epigenetics & Chromatin,
Год журнала:
2021,
Номер
14(1)
Опубликована: Июнь 3, 2021
Abstract
Background
DNA
methylation
is
an
epigenetic
chromatin
mark
that
allows
heterochromatin
formation
and
gene
silencing.
It
has
a
fundamental
role
in
preserving
genome
stability
(including
chromosome
stability)
by
controlling
both
expression
structure.
Therefore,
the
onset
of
incorrect
pattern
potentially
dangerous
for
cells.
This
particularly
important
with
respect
to
repetitive
elements,
which
constitute
third
human
genome.
Main
body
Repetitive
sequences
are
involved
several
cell
processes,
however,
due
their
intrinsic
nature,
they
can
be
source
instability.
Thus,
most
elements
usually
methylated
maintain
heterochromatic,
repressed
state.
Notably,
there
increasing
evidence
showing
(satellites,
long
interspersed
nuclear
(LINEs),
Alus)
frequently
hypomethylated
various
pathologies,
from
cancer
psychiatric
disorders.
sequences’
hypomethylation
correlates
relaxation
unscheduled
transcription.
If
these
alterations
directly
diseases
aetiology
how,
still
under
investigation.
Conclusions
Hypomethylation
different
families
recurrent
many
diseases,
suggesting
status
preservation
health.
provides
promising
point
view
towards
research
therapeutic
strategies
focused
on
specifically
tuning
repeats.
Cells,
Год журнала:
2022,
Номер
11(16), С. 2518 - 2518
Опубликована: Авг. 13, 2022
Mitochondria
are
not
only
the
main
energy
supplier
but
also
cell
metabolic
center
regulating
multiple
key
metaborates
that
play
pivotal
roles
in
epigenetics
regulation.
These
metabolites
include
acetyl-CoA,
α-ketoglutarate
(α-KG),
S-adenosyl
methionine
(SAM),
NAD+,
and
O-linked
beta-N-acetylglucosamine
(O-GlcNAc),
which
substrates
for
DNA
methylation
histone
post-translation
modifications,
essential
gene
transcriptional
regulation
fate
determination.
Tumorigenesis
is
attributed
to
many
factors,
including
mutations
tumor
microenvironment.
initiation,
evolution,
metastasis,
recurrence.
Targeting
mitochondrial
metabolism
promising
therapeutic
strategies
treatment.
In
this
review,
we
summarize
of
mitochondria
required
modification
discuss
current
strategy
cancer
therapies
via
targeting
epigenetic
modifiers
related
enzymes
This
review
an
important
contribution
understanding
metabolic-epigenetic-tumorigenesis
concept.
Clinical Epigenetics,
Год журнала:
2025,
Номер
17(1)
Опубликована: Янв. 16, 2025
Recent
studies
support
the
influence
of
paternal
lifestyle
and
diet
before
conception
on
health
offspring
via
epigenetic
inheritance
through
sperm
DNA
methylation,
histone
modification,
small
non-coding
RNA
(sncRNA)
expression
regulation.
Smoking
may
induce
hypermethylation
in
genes
related
to
anti-oxidation
insulin
resistance.
Paternal
obesity
are
associated
with
greater
risks
metabolic
dysfunction
alterations
sperm.
Metabolic
changes,
such
as
high
blood
glucose
levels
increased
body
weight,
commonly
observed
fathers
subjected
chronic
stress,
addition
an
enhanced
risk
depressive-like
behaviour
sensitivity
stress
both
F0
F1
generations.
methylation
is
correlated
quality
ability
fertilise
oocytes,
possibly
a
differentially
regulated
MAKP81IP3
signalling
pathway.
exposure
toxic
endocrine-disrupting
chemicals
(EDCs)
also
linked
transgenerational
transmission
predisposition
disease,
infertility,
testicular
disorders,
obesity,
polycystic
ovarian
syndrome
(PCOS)
females
changes
during
gametogenesis.
As
success
assisted
reproductive
technology
(ART)
affected
by
diet,
BMI,
alcohol
consumption,
its
outcomes
could
be
improved
modifying
factors
that
dependent
male
choices
environmental
factors.
This
review
discusses
importance
signatures
sperm—including
retention,
sncRNA—for
functionality,
early
embryo
development,
health.
We
discuss
mechanisms
which
(obesity,
smoking,
EDCs,
stress)
impact
epigenome.
Male
reproductive
health
is
governed
by
an
intricate
interplay
of
genetic,
epigenetic,
and
environmental
factors.
Epigenetic
mechanisms—encompassing
DNA
methylation,
histone
modifications,
non-coding
RNA
activity—are
crucial
both
for
spermatogenesis
sperm
maturation.
However,
oxidative
stress,
driven
excessive
reactive
oxygen
species,
disrupts
these
processes,
leading
to
impaired
function
male
infertility.
This
disruption
extends
epigenetic
resulting
in
abnormal
gene
expression
chromatin
remodeling
that
compromise
genomic
integrity
fertilization
potential.
Importantly,
oxidative-stress-induced
alterations
can
be
inherited,
affecting
the
fertility
offspring
future
generations.
review
investigates
how
stress
influences
regulation
reproduction
modifying
RNAs,
ultimately
compromising
spermatogenesis.
Additionally,
it
discusses
transgenerational
implications
disruptions
their
potential
role
hereditary
infertility
disease
predisposition.
Understanding
mechanisms
vital
developing
therapeutic
strategies
mitigate
damage
restore
homeostasis
germline.
By
integrating
insights
from
molecular,
clinical,
research,
this
work
emphasizes
need
targeted
interventions
enhance
prevent
adverse
outcomes
progeny.
Furthermore,
elucidating
dose–response
relationships
between
changes
remains
a
critical
research
priority,
informing
personalized
diagnostics
interventions.
In
context,
studies
should
adopt
standardized
markers
damage,
robust
clinical
trials,
multi-omic
approaches
capture
complexity
Such
rigorous
investigations
will
reduce
risk
disorders
optimize
outcomes.