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 azoos...

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Published in:Fertility and sterility 2014-08, Vol.102 (2), p.361-371.e5
Main Authors: Rondanino, Christine, Ph.D, Ouchchane, Lemlih, M.D., Ph.D, Chauffour, Candice, M.Sc, Marceau, Geoffroy, Pharm.D., Ph.D, Déchelotte, Pierre, M.D., Ph.D, Sion, Benoît, Pharm.D., Ph.D, Pons-Rejraji, Hanae, Ph.D, Janny, Laurent, M.D, Volle, David H., Ph.D, Lobaccaro, Jean-Marc A., Ph.D, Brugnon, Florence, M.D., Ph.D
Format: Article
Language:English
Subjects:
Apoptosis
Azoospermia
Azoospermia - genetics
Azoospermia - metabolism
Azoospermia - pathology
Azoospermia - physiopathology
Biopsy
Cell Proliferation
Fluorescent Antibody Technique
Gene Expression Regulation
Hospitals, University
human testis
Humans
Internal Medicine
Leydig Cells - chemistry
Life Sciences
lipid
Lipid Metabolism
Liver X Receptors
Male
Obstetrics and Gynecology
Orphan Nuclear Receptors - analysis
Orphan Nuclear Receptors - genetics
Prospective Studies
Reproductive Biology
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - analysis
Sperm Count
Spermatogenesis
Spermatozoa - chemistry
Spermatozoa - pathology
Testis - chemistry
Testis - pathology
Testis - physiopathology
Testosterone - biosynthesis
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Summary: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). Design Prospective study. Setting University hospital. Patient(s) Patients with various types of NOA (n = 22) and with OA (n = 5). Intervention(s) Human testicular biopsies. Main Outcome Measure(s) 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. Result(s) 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). Conclusion(s) Knowledge of changes in the transcript levels of LXR s and some of their downstream genes during altered spermatogenesis may help us to better understand the physiopathology of testicular failure in azoospermic patients.
ISSN:0015-0282
1556-5653
DOI:10.1016/j.fertnstert.2014.04.033