in male fertiliry 25 Avril 2012 David VOLLE CR1 Inserm UMR Génétique Reproduction amp Développement Inserm U1103 UMR CNRS 6293 Clermont Université Some points publication 2012 ID: 774639
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Slide1
Lipid nuclear receptors in male fertiliry
25 Avril 2012
David VOLLECR1 InsermUMR Génétique Reproduction & Développement Inserm U1103, UMR CNRS 6293, Clermont Université
Slide2Some
points (publication 2012)
Infertility
…
50% of the case male is involved
25% of couples are steriles (1year)
Carlsen et al: 61 articles de 1938 à 1990 Swan et al: 101 articles de 1934 à 1996
Obstructive
azoospermia
Secretory azoospermia
Spermatozoa quality…
In 30% of male infertility, the origin remains unknown
ART
from testicular spermatozoa
There
is
a need to better define characteristics of germ cell differentiation
Slide3Germ
cells
Spermatogonia→ spermatocytes → spermatides → spz…
1 -
prolifération
3 -
spermiogenesis
2 -
meisosi
Endocrine
function
(
interstitial
space
)
Exocrine
function
Leydig
Testosterone
synthesis
Sertoli
Support
de of
gametogenesis
n=6
n=6
Témoin
4 mois
Master II
Testicular
ohysiology
Slide4Cellule de Sertoli
Cellule de Leydig
Hypothalamo
-
Pituitary
axis
Testosterone
Slide5Local regulation of testicular function
Nuclear receptor superfamily
Slide6Slide7Lack
of
LXRs
leads to male
infertility
Thje
Liver X Receptors a and b
Volle
et al
. Mol
Endocrinol
. 2007
Slide8Leydig
Germ
cells
Sertoli
Volle
et al
. Mol
Endocrinol
. 2007
Slide9The Small Heterodimer PartnerIn adult testis
Lhcgr
Fsh
Shp
Testosterone
Volle
et a
l.
Genes
& Dev 2007
Slide10SHP in neonatal
Complexity
of the impact on
testicular
physiology
Volle
et al
.
Genes
& Dev 2007
Slide11A model for the
role
of SHP in testis
Volle
et al.
Genes
& Dev 2007
Slide12Shp
and
estrogenic endocrine disrupters
Shp
a
molecular link between estrogenic endocrine disrupters and tesis physiology
Volle
et a
l. JCI 2009
Slide13Shp
and
estrogenic endocrine disrupters
Shp acts through retinoid/G9a pathway
Volle
et al
. JCI 2009
Slide14Shp
and estrogenic endocrine disrupters
Shp does not control neonatal steroidogenesis
Slide15A more
complex
model
than
expected
Slide16Complexity of the impact on testicular physiology
Cell
type
where
NR
is
expressed
Slide17Maqdasy
et al
. MCE 2013
Slide18Complexity of the impact on testicular physiology
Cell type where NR is expressed
When NR is expressed
Potential
links
between
Eds
and male
disorders
Slide19Identification of etiology of infertility
Perspectives
Polymorphisms
Potential
therapeutical
targets
Slide20Thanks
for
your
attention