Children,
Journal Year:
2023,
Volume and Issue:
10(4), P. 737 - 737
Published: April 17, 2023
Cryptorchidism,
defined
as
the
failure
of
at
least
one
or
both
testicles
to
descend
into
scrotal
pouches,
is
most
frequent
(1.6-9%
birth,
1/20
males
birth)
congenital
anomaly
encountered
in
newborn
males,
resulting
causes
non-obstructive
azoospermia
men.
Similar
other
malformations,
cryptorchidism
thought
be
caused
by
endocrine
and
genetic
factors,
combined
with
maternal
environmental
influences.
The
etiology
unknown,
it
involves
complex
mechanisms
aiming
control
testicular
development
descent
from
their
initial
intra-abdominal
location
pouches.
implication
insulin-like
3
(INSL-3)
associated
its
receptor
(LGR8)
critical.
Genetic
analysis
discloses
functionally
deleterious
mutations
INSL3
GREAT/LGR8
genes.
In
this
literature
review,
we
discuss
analyze
INSL3/LGR8
mutation
occurrence
human
animal
models.
Life,
Journal Year:
2023,
Volume and Issue:
13(5), P. 1093 - 1093
Published: April 27, 2023
The
group
of
disorders
known
as
46,XY
gonadal
dysgenesis
(GD)
is
characterized
by
anomalies
in
testis
determination,
including
complete
and
partial
GD
(PGD)
testicular
regression
syndrome
(TRS).
Several
genes
are
to
be
involved
sex
development
pathways,
however
approximately
50%
all
cases
remain
elusive.
Recent
studies
have
identified
variants
Proceedings of the National Academy of Sciences,
Journal Year:
2024,
Volume and Issue:
121(7)
Published: Feb. 5, 2024
Cryptorchidism
is
the
most
common
form
of
disorder
sex
development
in
male
dogs,
but
its
hereditary
predisposition
poorly
elucidated.
The
gonadal
transcriptome
nine
unilaterally
cryptorchid
dogs
and
seven
control
was
analyzed
using
RNA-seq.
Comparison
between
scrotal
inguinal
gonads
unilateral
revealed
8,028
differentially
expressed
genes
(DEGs)
(3,377
up-regulated
4,651
down-regulated).
A
similar
number
DEGs
(7,619)
found
by
comparing
undescended
testicles
with
descended
dogs.
methylation
status
selected
also
analyzed,
three
out
studied
showing
altered
patterns.
Bioinformatic
analysis
cDNA
sequences
20,366
SNP
variants,
six
which
showed
significant
differences
allelic
counts
Validation
studies
larger
cohorts
(
n
=
122)
173)
that
TT
genotype
(rs850666472,
p.Ala1230Val)
AA
3′UTR
(16:23716202G>A)
KATA6
,
responsible
for
acetylation
lysine
9
histone
H3,
are
associated
cryptorchidism
P
0.0383).
Both
transcript
level
KAT6A
H3K9
were
lower
testes,
additionally,
depended
on
genotypes
exon
17
3′UTR.
Our
study
massive
alteration
not
caused
germinal
DNA
variants
DEG
regulatory
partly
an
aberrant
Moreover,
can
be
considered
markers
risk
this
disorder.
Human Reproduction,
Journal Year:
2023,
Volume and Issue:
38(7), P. 1412 - 1423
Published: May 19, 2023
Abstract
STUDY
QUESTION
What
is
the
impact
of
variants
in
genes
INSL3
(Insulin
Like
3)
and
RXFP2
(Relaxin
Family
Peptide
Receptor
2),
respectively,
on
cryptorchidism
male
infertility?
SUMMARY
ANSWER
Bi-allelic
loss-of-function
(LoF)
result
bilateral
infertility,
whereas
heterozygous
variant
carriers
are
phenotypically
unaffected.
WHAT
IS
KNOWN
ALREADY
The
small
heterodimeric
peptide
its
G
protein-coupled
receptor
play
a
major
role
first
step
biphasic
descent
testes,
have
long
been
implicated
inherited
cryptorchidism.
However,
only
one
single
homozygous
missense
has
clearly
linked
to
familial
cryptorchidism,
so
effects
bi-allelic
both
infertility
remain
unclear.
DESIGN,
SIZE,
DURATION
Exome
data
2412
men
from
MERGE
(Male
Reproductive
Genomics)
study
cohort
including
1902
infertile
with
crypto-/azoospermia,
whom
450
had
history
were
screened
for
high-impact
RXFP2.
PARTICIPANTS/MATERIALS,
SETTING,
METHODS
For
patients
rare,
RXFP2,
detailed
clinical
collected
testicular
phenotype
was
determined.
Genotyping
family
members
performed
analyse
co-segregation
candidate
condition.
Immunohistochemical
staining
patient
tissue
measuring
serum
concentration
functional
INSL3.
protein’s
cell
surface
expression
ability
respond
CRE
reporter
gene
assay
MAIN
RESULTS
AND
THE
ROLE
OF
CHANCE
This
presents
correlates
these
Functional
identified
demonstrated
by
absence
INSL3-specific
patients’
Leydig
cells
as
well
undetectable
blood
levels.
lead
reduced
mediated
activation.
LIMITATIONS,
REASONS
FOR
CAUTION
Further
investigations
needed
explore
potential
direct
spermatogenesis.
With
our
data,
we
cannot
determine
whether
observed
consequence
disruption
possible
function
spermatogenesis
or
it
occurs
secondarily
due
WIDER
IMPLICATIONS
FINDINGS
In
contrast
previous
assumptions,
this
supports
an
autosomal
recessive
inheritance
INSL3-
RXFP2-related
while
LoF
either
can
at
most
be
regarded
risk
factor
developing
Our
findings
diagnostic
value
familial/bilateral
additionally
shed
light
importance
fertility.
FUNDING/COMPETING
INTEREST(S)
carried
out
within
frame
German
Research
Foundation
(DFG)
funded
Clinical
Unit
‘Male
Germ
Cells:
Genes
Function’
(DFG,
CRU326).
Florey
supported
NHMRC
grant
(2001027)
Victorian
Government
Operational
Infrastructure
Support
Program.
A.S.B.
DFG
(‘Emmy
Noether
Programme’
project
number
464240267).
authors
declare
no
conflict
interest.
TRIAL
REGISTRATION
NUMBER
N/A.
Hormone Research in Paediatrics,
Journal Year:
2024,
Volume and Issue:
unknown, P. 1 - 8
Published: Feb. 15, 2024
<b><i>Introduction:</i></b>
The
testicular
regression
syndrome
(TRS)
is
a
form
of
differences
sex
development
(DSD)
in
which
the
testes
differentiate
and
function
during
early
embryonic
development,
but
subsequently
regress.
clinical
phenotype
TRS
often
overlaps
with
that
partial
gonadal
dysgenesis
(PGD).
Previous
studies
have
demonstrated
causal
association
between
TRS/PGD
heterozygous
missense
variants
<i>DHX37</i>.
<b><i>Methods:</i></b>
We
enrolled
11
Japanese
46,XY
individuals
(from
10
families)
who
exhibited
undetected
or
hypoplastic
testes,
Müllerian
duct
regression,
low
serum
testosterone
anti-Müllerian
hormone
levels.
subjects
underwent
targeted
sequencing
36
known
causative
genes
for
DSD,
PCR-based
Sanger
<i>DHX37</i>,
whole-exome
sequencing.
<b><i>Results:</i></b>
Previously
described
pathogenic
novel
nonsense
(<i>SRY</i>,
<i>NR5A1</i>,
<i>DMRT1</i>)
were
observed
four
out
families.
Additionally,
we
identified
two
rare
<i>DHX37</i>
families:
previously
reported
variant
(c.923G>A,
p.Arg308Gln)
three
likely
(c.1882A>C,
p.Thr628Pro)
one.
external
genitalia
patients
varied
from
female-type
to
male-type
without
micropenis.
Eighty
percent
had
monogenic
disorders
including
being
most
commonly
(40%).
internal
genital
carriers
others.
<b><i>Conclusions:</i></b>
one
common
genetic
causes
derivatives.
Genetic
test
helpful
detecting
<i>DHX37</i>-related
because
phenotypic
diversity
this
disorder.
Frontiers in Endocrinology,
Journal Year:
2024,
Volume and Issue:
15
Published: April 9, 2024
RASopathies
are
syndromes
caused
by
congenital
defects
in
the
Ras/mitogen-activated
protein
kinase
(MAPK)
pathway
genes,
with
a
population
prevalence
of
1
1,000.
Patients
typically
identified
childhood
based
on
diverse
characteristic
features,
including
cryptorchidism
(CR)
>50%
affected
men.
As
CR
predisposes
to
spermatogenic
failure
(SPGF;
total
sperm
count
per
ejaculate
0–39
million),
we
hypothesized
that
men
seeking
infertility
management
include
cases
undiagnosed
RASopathies.
Likely
pathogenic
or
(LP/P)
variants
22
RASopathy-linked
genes
were
screened
521
idiopathic
SPGF
patients
(including
155
cases)
and
323
normozoospermic
controls
using
exome
sequencing.
All
844
recruited
ESTonian
ANDrology
(ESTAND)
cohort
underwent
identical
andrological
phenotyping.
RASopathy-specific
variant
interpretation
guidelines
used
for
pathogenicity
assessment.
LP/P
PTPN11
(two),
SOS1
(three),
SOS2
(one),
LZTR1
SPRED1
NF1
MAP2K1
(one).
The
findings
six
SPGF,
three
366
only,
one
(of
323)
subfertile
man.
subgroup
“CR
SPGF”
had
over
13-fold
enrichment
compared
(3.9%
vs.
0.3%;
Fisher’s
exact
test,
p
=
5.5
×
10
−3
).
ESTAND
subjects
Ras/MAPK
presented
genitourinary
anomalies,
skeletal
joint
conditions,
other
health
concerns.
Rare
forms
malignancies
(schwannomatosis
pancreatic
testicular
cancer)
reported
four
occasions.
Genetics
Male
Infertility
Initiative
(GEMINI)
(1,416
317
fertile
men)
was
validate
outcome.
MRAS
(one)
4/31
GEMINI
CR)
Undiagnosed
detected
17
subjects,
15
(10
CR),
two
Affected
RASopathy
showed
high
expression
somatic
cells.
In
conclusion,
represent
new
etiology
syndromic
male
infertility.
especially
enriched
among
history
cryptorchidism.
Given
relationship
between
infertile
found
have
this
molecular
diagnosis
should
be
evaluated
known
concerns,
specific
rare
malignancies.
Acta Paediatrica,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 14, 2025
ABSTRACT
Aim
The
therapeutic
approach
to
differences
of
sex
development
(DSD)
has
changed
over
recent
decades.
We
aimed
describe
the
evolution
clinical
diagnoses
DSD
in
children
attending
a
tertiary
paediatric
centre.
Methods
This
retrospective
observational
study
compared
and
management,
before
after
introduction
consensus
guidelines
for
2006.
Results
cohort
included
87
patients
with
46,
XY
(78.4%),
15
XX
(13.5%)
9
chromosomal
(8.1%).
Gonadectomy
rates
were
27.9%,
6.6%
66.6%
respective
groups.
mean
age
at
presentation
was
younger
among
those
than
(0.5
±
2.5
vs.
6.8
8.1
years,
p
=
0.007)
higher
proportion
presented
by
one
year
(93.1%
60.0%,
0.001).
During
1990–2006,
44
diagnosed,
during
2007–2019,
67
children.
Prenatal
diagnosis
increased
from
4.5%
25.4%
(
0.004).
Smaller
proportions
later
earlier
period
underwent
gonadectomy
(19.4%
40.9%,
0.017)
reassignment
(1.5%
13.6%,
<
0.02).
Conclusion
Over
three‐decade
period,
rate
prenatal
declined.
These
findings
reflect
shift
towards
earlier,
individualised
multidisciplinary
care,
which
facilitated
advanced
diagnostics.
Russian Journal of Pediatric Surgery,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 15, 2025
According
to
domestic
and
foreign
literature,
nonpalpable
testes
(NPT)
are
found
in
20%
of
children
with
cryptorchidism.
Approximately
50%
them
located
the
abdominal
cavity,
atrophied
or
vanished
testes.
The
aim
our
review
is
systematize
scientific
literature
data
on
testis
syndrome
children.
Materials
Methods.
composed
original
articles
databases
such
as
eLibrary,
PubMed,
Scopus.
Results
Discussions.
In
often
classified
into
three
types:
intra-abdominal,
extra-abdominal,
non-viable.
Extra-abdominal
gonads
more
normal
volume
compared
intra-abdominal
ones,
which
mostly
hypoplastic.
There
many
controversial
issues
regarding
diagnostic
methods
treatment
strategies
for
different
types
NPT
Conclusions.
problem
diagnosing
treating
children,
especially
cases
high
localization
gonad,
remains
highly
relevant
requires
further
research
observations.
BMC Genomics,
Journal Year:
2025,
Volume and Issue:
26(1)
Published: Feb. 19, 2025
Cryptorchidism
is
one
of
the
most
common
reproductive
abnormalities
in
rams,
which
seriously
harms
capacity
rams
and
causes
significant
economic
losses
to
sheep
industry.
However,
there
are
few
studies
elucidating
its
hereditary
predisposition
sheep.
In
present
study,
transcriptome
proteome
cryptic
(CT)
contralateral
(CLT)
testis
from
four
unilaterally
cryptorchid
normal
(NT)
healthy
were
analyzed
using
RNA-seq
TMT-based
proteomics,
respectively.
A
total
10,357,
10,175,
132
differentially
expressed
genes
(DEGs)
identified
between
CT
vs.
CLT,
NT,
CLT
NT.
Venn
diagram
showed
that
9744
DEGs
(5499
up-regulated
4245
down-regulated)
shared
Functional
enrichment
analysis
revealed
5499
mainly
involved
regulation
programmed
cell
death
metabolic
process,
while
down-regulated
closely
related
such
as
spermatogenesis,
sexual
reproduction,
reproduction
male
gamete
generation.
Furthermore,
325
overlapped
(114
211
DAPs
same
regulatory
status
by
combining
transcriptomics
proteomics.
Ten
genes,
including
AKAP4,
AKAP3,
FSIP2,
HSPA1L,
HSPA4L,
TUBB,
TXNRD2,
CDC42,
PGK1
HSPA1A,
candidate
key
unilateral
cryptorchidism.
Our
results
both
gene
protein
expression
massively
altered.
Bioinformatics
unveiled
several
signaling
pathways
potentially
These
findings
provide
new
insights
into
molecular
mechanism
underlying
spermatogenesis
failure
caused