Absence of nuclear receptors for oxysterols liver X receptor induces ovarian hyperstimulation syndrome in mice.
Ovarian hyperstimulation syndrome is a frequent complication occurring during in vitro fertilization cycles. It is characterized by a massive ovarian enlargement associated with an accumulation of extra vascular fluid. Here we show that liver X receptor (LXR)-alpha and LXR-beta deficient mice present many clinical and biological signs of ovarian hyperstimulation syndrome: ovarian enlargement, hemorrhagic corpora lutea, increased ovarian vascular permeability, and elevated estradiol. Ovulation stimulation resulted in excessive ovarian response to exogenous gonadotropins because follicle number and estradiol production were higher in transgenic mice. LXR deficiency also leads to perturbations in general inflammatory status, associated with ovarian il-6 deregulation. Upon treatment with the synthetic LXR agonist T09101317, serum estradiol and expression of star and cyp11a1 genes were markedly increased in wild-type mice, showing that LXRs are key regulators of ovarian steroidogenesis. These results suggest that LXRs control the ovulation by regulating endocrine and vascular processes.
Mouzat
Kevin
K
Unité Mixte de Recherche, Centre National de la Recherche Scientifique 6247, Clermont Université, Centre de Recherche en Nutrition Humaine d'Auvergne, 63177 Aubière Cedex, France.
Volat
Fanny
F
Baron
Silvère
S
Alves
Georges
G
Pommier
Aurélien J C
AJ
Volle
David H
DH
Marceau
Geoffroy
G
DeHaze
Angélique
A
Déchelotte
Pierre
P
Duggavathi
Raj
R
Caira
Françoise
F
Lobaccaro
Jean-Marc A
JM