Levels of liver x receptors in testicular biopsies of patients with azoospermia

Capsule:
This study shows differences in mRNA levels of the transcription factors LXRs and some of their downstream genes in testes of men with nonobstructive azoospermia and obstructive azoospermia.

Authors:
Christine Rondanino, Ph.D., Lemlih Ouchchane, M.D., Ph.D., Candice Chauffour, M.Sc., Geoffroy Marceau, PharmD., Ph.D., Pierre Déchelotte, M.D., Ph.D., Benoît Sion, PharmD., Ph.D., Hanae Pons-Rejraji, Ph.D., Laurent Janny, M.D., David H Volle, Ph.D., Jean-Marc A Lobaccaro, Ph.D., Florence Brugnon, M.D., PhD.

Volume 102, Issue 2, Pages 361–371.e5

Abstract:

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 LXRs and some of their downstream genes during altered spermatogenesis may help us to better understand the physiopathology of testicular failure in azoospermic patients.

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