Levels of liver X receptors in testicular biopsies of patients with azoospermia.
OBJECTIVE
To determine whether the transcription factors liver X receptors (LXRs) and their downstream genes, which are involved in the regulation of several testicular functions in mouse models, are differentially expressed in testes of men with nonobstructive azoospermia (NOA) or obstructive azoospermia (OA).


METHODS
Prospective study.


METHODS
University hospital.


METHODS
Patients with various types of NOA (n=22) and with OA (n=5).


METHODS
Human testicular biopsies.


METHODS
Transcript levels were measured in testicular biopsies with the use of quantitative polymerase chain reaction. Correlations of LXR mRNA levels with the number of germ cells, the expression of proliferation and apoptosis markers, and the amount of intratesticular lipids and testosterone were evaluated. The localization of LXRα was analyzed by immunofluorescence.


RESULTS
LXR mRNA levels were decreased by 49%-98% in NOA specimens and positively correlated with germ cell number. Accumulations of IDOL and SREBP1c (LXR targets involved in lipid homeostasis) were 1.8-2.1 times lower in NOA samples and mRNA levels of the SREBP1c target gene ELOVL6 were increased 1.9-2.4-fold. Interestingly, the amount of triglycerides and free fatty acids were higher in NOA testes (3.4-12.2-fold). LXRα was present in Leydig cells. Accumulations of LXR downstream genes encoding the steroidogenic proteins StAR and 3βHSD2 were higher in NOA testes (5.9-12.8-fold).


CONCLUSIONS
Knowledge of changes in the transcript levels of LXRs and some of their downstream genes during altered spermatogenesis may help us to better understand the physiopathology of testicular failure in azoospermic patients.
Génétique Reproduction et Développement, Clermont Université, Clermont-Ferrand, France; CNRS, UMR 6293, GReD, Aubière, France; INSERM, UMR 1103, GReD, Aubière, France; Centre de Recherche en Nutrition Humaine d'Auvergne, Clermont-Ferrand, France; AMP-CECOS, CHU Clermont-Ferrand, CHU Estaing, Clermont-Ferrand, France.
Christine
C
Rondanino
Laboratoire ISIT, UMR 6284 Université d'Auvergne-CNRS, Clermont-Ferrand, France; Service de Biostatistiques, Clermont-Ferrand, France.
Lemlih
L
Ouchchane
Génétique Reproduction et Développement, Clermont Université, Clermont-Ferrand, France; CNRS, UMR 6293, GReD, Aubière, France; INSERM, UMR 1103, GReD, Aubière, France; Centre de Recherche en Nutrition Humaine d'Auvergne, Clermont-Ferrand, France; AMP-CECOS, CHU Clermont-Ferrand, CHU Estaing, Clermont-Ferrand, France.
Candice
C
Chauffour
Laboratoire de Biochimie, CHU Clermont-Ferrand, Clermont-Ferrand, France.
Geoffroy
G
Marceau
Service d'Anatomie Pathologique, CHU Clermont-Ferrand, CHU Estaing, Clermont-Ferrand, France.
Pierre
P
Déchelotte
Laboratoire NEURO-DOL, INSERM U 1107, Clermont-Ferrand, France; Laboratoire de Pharmacologie Fondamentale et Clinique de la Douleur, Université d'Auvergne, Clermont-Ferrand, France.
Benoît
B
Sion
Génétique Reproduction et Développement, Clermont Université, Clermont-Ferrand, France; CNRS, UMR 6293, GReD, Aubière, France; INSERM, UMR 1103, GReD, Aubière, France; AMP-CECOS, CHU Clermont-Ferrand, CHU Estaing, Clermont-Ferrand, France.
Hanae
H
Pons-Rejraji
Génétique Reproduction et Développement, Clermont Université, Clermont-Ferrand, France; CNRS, UMR 6293, GReD, Aubière, France; INSERM, UMR 1103, GReD, Aubière, France; AMP-CECOS, CHU Clermont-Ferrand, CHU Estaing, Clermont-Ferrand, France.
Laurent
L
Janny
Génétique Reproduction et Développement, Clermont Université, Clermont-Ferrand, France; CNRS, UMR 6293, GReD, Aubière, France; INSERM, UMR 1103, GReD, Aubière, France; Centre de Recherche en Nutrition Humaine d'Auvergne, Clermont-Ferrand, France.
David H
DH
Volle
Génétique Reproduction et Développement, Clermont Université, Clermont-Ferrand, France; CNRS, UMR 6293, GReD, Aubière, France; INSERM, UMR 1103, GReD, Aubière, France; Centre de Recherche en Nutrition Humaine d'Auvergne, Clermont-Ferrand, France.
Jean-Marc A
JM
Lobaccaro
Génétique Reproduction et Développement, Clermont Université, Clermont-Ferrand, France; CNRS, UMR 6293, GReD, Aubière, France; INSERM, UMR 1103, GReD, Aubière, France; AMP-CECOS, CHU Clermont-Ferrand, CHU Estaing, Clermont-Ferrand, France. Electronic address: fbrugnon@chu-clermontferrand.fr.
Florence
F
Brugnon
D017209:Apoptosis; D053713:Azoospermia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001706:Biopsy; D049109:Cell Proliferation; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006785:Hospitals, University; D006801:Humans; D007985:Leydig Cells / Q000737:chemistry; D050356:Lipid Metabolism; D000071518:Liver X Receptors; D008297:Male; D057093:Orphan Nuclear Receptors / Q000032:analysis* / Q000235:genetics; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013076:Sperm Count; D013091:Spermatogenesis; D013094:Spermatozoa / Q000737:chemistry / Q000473:pathology; D013737:Testis / Q000737:chemistry* / Q000473:pathology / Q000503:physiopathology; D013739:Testosterone / Q000096:biosynthesis
D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D013739:Testosterone
Azoospermia; human testis; lipid; liver X receptors; spermatogenesis