bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 13, 2024
The
voltage-
and
pH-gated
Slo3
potassium
channel
is
exclusively
expressed
in
mammalian
spermatozoa.
Its
sensitivity
to
both
voltage
alkalization
plays
a
crucial
role
sperm
fertility,
which
tightly
coupled
the
capacitation
process.
Here
we
show
that
sperm-enriched
divalent
cation
Zn
2+
undergoes
dynamic
alteration
spermatozoa
during
capacitation.
We
also
found
intracellular
regulates
alkalinization-induced
hyperpolarization
mice
mediated
by
channel.
Further
examination
of
zinc
regulation
mouse
(mSlo3)
revealed
that,
Xenopus
oocyte
expression
system,
directly
inhibits
currents
dose-dependent
manner
at
micromolar
concentrations,
with
exceptionally
slow
dissociation.
By
combining
MD
simulations
electrophysiology,
identified
amino
acid
residues
contributing
dissociation
from
channels.
Our
studies
uncover
importance
dynamics
its
regulatory
ion
channels
Human Reproduction,
Journal Year:
2024,
Volume and Issue:
39(4), P. 674 - 688
Published: Feb. 14, 2024
Abstract
STUDY
QUESTION
Whether
and
how
do
Na+/H+
exchangers
(NHEs)
regulate
the
physiological
functions
of
human
sperm?
SUMMARY
ANSWER
NHE-mediated
flagellar
intracellular
pH
(pHi)
homeostasis
facilitates
activation
pH-sensitive,
sperm-specific
Ca2+
channel
(CatSper)
K+
(KSper),
which
subsequently
modulate
sperm
motility,
hyperactivation,
tyrosine
phosphorylation,
progesterone
(P4)-induced
acrosome
reaction.
WHAT
IS
KNOWN
ALREADY
Sperm
pHi
alkalization
is
an
essential
prerequisite
for
acquisition
sperm-fertilizing
capacity.
Different
are
strictly
controlled
by
particular
regulatory
mechanisms.
NHEs
suggested
to
H+
efflux.
DESIGN,
SIZE,
DURATION
This
was
a
laboratory
study
that
used
samples
from
>50
donors
over
period
1
year.
To
evaluate
NHE
action
on
function,
5-(N,N-dimethyl)-amiloride
(DMA),
highly
selective
inhibitor
NHEs,
utilized.
All
experiments
were
repeated
at
least
five
times
using
different
individual
or
cells.
PARTICIPANTS/MATERIALS,
SETTING,
METHODS
By
utilizing
fluorescent
indicator
pHrodo
Red-AM,
we
detected
alterations
in
single-cell
value
sperm.
The
currents
CatSper
KSper
recorded
whole-cell
patch-clamp
technique.
Changes
population
concentrations
([Ca2+]i)
loaded
with
Fluo
4-AM
measured.
Membrane
potential
(Vm)
quantitatively
examined
multimode
plate
reader
after
3,3′-dipropylthiadicarbocyanine
iodide
2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein,
acetoxymethyl
ester,
respectively.
motility
parameters
assessed
computer-assisted
semen
analysis
system.
Tyrosine
phosphorylation
determined
immunofluorescence,
reaction
evaluated
Pisum
sativum
agglutinin-FITC
staining.
MAIN
RESULTS
AND
THE
ROLE
OF
CHANCE
DMA-induced
inhibition
severely
acidified
7.20
±
0.04
6.38
0.12
(mean
SEM),
while
effect
DMA
acrosomal
less
obvious
(from
5.90
0.13
5.57
0.12,
mean
SEM).
recordings
revealed
remarkably
suppressed
alkalization-induced
KSper.
As
consequence,
impairment
[Ca2+]i
Vm
maintenance
presence
DMA.
During
capacitation
process,
pre-treatment
2
h
potently
decreased
pHi,
turn
kinetic
parameters.
capacitation-associated
functions,
including
P4-induced
reaction,
also
compromised
inhibition.
LARGE
SCALE
DATA
N/A.
LIMITATIONS,
REASONS
FOR
CAUTION
vitro
study.
Caution
should
be
taken
when
extrapolating
these
results
vivo
applications.
WIDER
IMPLICATIONS
FINDINGS
important
regulators
KSper,
indispensable
fertility,
suggesting
malfunction
could
underlying
mechanism
pathogenesis
male
infertility.
FUNDING/COMPETING
INTEREST(S)
work
supported
National
Natural
Science
Foundation
China
(32271167
81871202
X.Z.),
Jiangsu
Innovation
Entrepreneurship
Talent
Plan
(JSSCRC20211543
Social
Development
Project
Province
(No.
BE2022765
Society
livelihood
Nantong
City
MS22022087
(BK20220608
H.K.).
authors
have
no
competing
interests
declare.
Cells,
Journal Year:
2024,
Volume and Issue:
13(10), P. 865 - 865
Published: May 17, 2024
As
in
most
cells,
intracellular
pH
regulation
is
fundamental
for
sperm
physiology.
Key
functions
like
swimming,
maturation,
and
a
unique
exocytotic
process,
the
acrosome
reaction,
necessary
gamete
fusion,
are
deeply
influenced
by
pH.
Sperm
regulation,
both
intracellularly
within
organelles
such
as
acrosome,
requires
coordinated
interplay
of
various
transporters
channels,
ensuring
that
this
cell
primed
fertilization.
Consistent
with
pivotal
importance
mammalian
physiology,
several
its
dependent
on
cytosolic
Examples
include
Ca
Molecular Reproduction and Development,
Journal Year:
2025,
Volume and Issue:
92(1)
Published: Jan. 1, 2025
ABSTRACT
Odourant
receptors
(ORs)
are
not
restricted
only
to
the
nose,
but
also
occur
in
many
other
organs
and
tissues,
including
reproductive
system.
In
fact,
ORs
most
heavily
expressed
testis
than
any
extra‐nasal
tissue.
Accumulating
evidence
suggests
that
olfactory
systems
both
structurally
functionally
linked
these
interconnections
can
influence
various
aspects
of
reproduction.
this
article,
we
first
review
our
current
understanding
then
collate
accumulated
on
presence
male
system
sperm
cells.
We
investigate
potential
role
female
tract
odourants
chemotaxis
selection.
Finally,
since
existing
especially
for
odor
sensing
capability
its
physiological
function
controversial,
reasons
controversy
propose
some
ways
resolve
debate.
Collectively,
conclude
odourant
signaling
may
play
an
important,
although
currently
largely
unclear
key
processes
directly
related
fertility.
However,
lack
holistic
functional
significance
pathways
system,
more
empirical
research
is
warranted.
British Journal of Pharmacology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 27, 2025
Loss
of
function
the
sperm-specific
Ca2+
channel
CatSper
is
a
common
channelopathy
that
causes
male
infertility.
controls
intracellular
concentration
and,
thereby,
motility
human
sperm.
Activation
by
oviductal
ligands
evokes
transient
increase,
which
entails
changes
in
flagellar
beat
are
required
for
fertilisation.
The
CatSper-mediated
influx
has
been
studied
extensively,
whereas
mechanisms
underlying
clearance
and
recovery
from
have
remained
ill-defined.
We
examined
how
pharmacological
suppression
export
cytosol
into
extracellular
space
or
uptake
stores
affects
resting
signals
sperm
healthy
volunteers
infertile
men
lacking
functional
channels,
using
kinetic
Ca2+-
pH-fluorometry
as
well
patch-clamp
recordings.
show
entering
via
predominantly,
if
not
exclusively,
exported
plasma
membrane
ATPases
(PMCAs).
Na+/Ca2+
exchange
mitochondria
play
no
only
negligible
role
signalling
controlled
interplay
PMCAs,
is,
balance
between
The
voltage-
and
pH-gated
Slo3
potassium
channel
is
exclusively
expressed
in
mammalian
spermatozoa.
Its
sensitivity
to
both
voltage
alkalization
plays
a
crucial
role
sperm
fertility,
which
tightly
coupled
the
capacitation
process.
Here
we
show
that
sperm-enriched
divalent
cation
Zn
2+
undergoes
dynamic
alteration
spermatozoa
during
capacitation.
We
also
found
intracellular
regulates
alkalinization-induced
hyperpolarization
mice
mediated
by
channel.
Further
examination
of
zinc
regulation
mouse
(mSlo3)
revealed
that,
Xenopus
oocyte
expression
system,
directly
inhibits
currents
dose-dependent
manner
at
micromolar
concentrations,
with
exceptionally
slow
dissociation.
By
combining
MD
simulations
electrophysiology,
identified
amino
acid
residues
contributing
dissociation
from
channels.
Our
studies
uncover
importance
dynamics
its
regulatory
ion
channels
The
voltage-
and
pH-gated
Slo3
potassium
channel
is
exclusively
expressed
in
mammalian
spermatozoa.
Its
sensitivity
to
both
voltage
alkalization
plays
a
crucial
role
sperm
fertility,
which
tightly
coupled
the
capacitation
process.
Here
we
show
that
sperm-enriched
divalent
cation
Zn
2+
undergoes
dynamic
alteration
spermatozoa
during
capacitation.
We
also
found
intracellular
regulates
alkalinization-induced
hyperpolarization
mice
mediated
by
channel.
Further
examination
of
zinc
regulation
mouse
(mSlo3)
revealed
that,
Xenopus
oocyte
expression
system,
directly
inhibits
currents
dose-dependent
manner
at
micromolar
concentrations,
with
exceptionally
slow
dissociation.
By
combining
MD
simulations
electrophysiology,
identified
amino
acid
residues
contributing
dissociation
from
channels.
Our
studies
uncover
importance
dynamics
its
regulatory
ion
channels
Reproductive Medicine and Biology,
Journal Year:
2024,
Volume and Issue:
23(1)
Published: Jan. 1, 2024
Mammalian
spermatozoa
have
to
be
"capacitated"
fertilization-competent.
Capacitation
is
a
collective
term
for
the
physiological
and
biochemical
changes
in
that
occur
within
female
body.
However,
regulatory
mechanisms
underlying
capacitation
not
been
fully
elucidated.
Journal of Experimental Biology,
Journal Year:
2024,
Volume and Issue:
227(6)
Published: Feb. 21, 2024
ABSTRACT
From
bacteria
to
metazoans,
higher
density
populations
have
lower
per
capita
metabolic
rates
than
populations.
The
negative
covariance
between
population
and
rate
is
thought
represent
a
form
of
adaptive
plasticity.
A
relationship
metabolism
was
actually
first
noted
100
years
ago,
focused
on
spermatozoa;
even
then,
it
postulated
that
plasticity
drove
this
pattern.
Since
contemporary
studies
sperm
specifically
assume
concentration
has
no
effect
show
We
did
systematic
review
estimate
the
aerobic
concentration,
for
198
estimates
spanning
49
species,
from
protostomes
humans
88
studies.
found
strong
evidence
are
dependent:
both
within
among
metabolisms
in
dense
ejaculates,
but
increase
their
when
diluted.
On
average,
10-fold
decrease
increased
by
35%.
Metabolic
appears
be
an
response,
whereby
maximize
chances
encountering
eggs.
