Impaired secretion of C-X-C motif chemokine ligand 10 by stimulation with a Toll-like receptor 4 ligand in endometrial epithelium of infertile patients with minimal-to-mild endometriosis.

Successful embryo implantation requires transient, well-controlled inflammation in decidualizing cells. In mice, Toll-like receptor (TLR) 4 signaling in endometrial epithelial cells (EECs) by stimulation with factors present in seminal fluids has been shown to be a key upstream driver of a controlled inflammatory response. Clinical evidence supports that exposure of the female reproductive tract to seminal plasma promotes implantation success. We investigated the response of EECs to TLR2 (Pam3Csk4), TLR 3 (Poly I:C), and TLR4 (lipopolysaccharides [LPS]) ligands with respect to secretion of C-X-C motif chemokine ligand (CXCL) 10 (CXCL10) and interleukin-6 (IL-6) in infertile patients with minimal-to-mild endometriosis (EECs-endo) (n = 38) and those of healthy, fertile women (EECs-healthy) (n = 30). Stimulation with either Pam3Csk4, Poly I:C or LPS, significantly induced CXCL10 and IL-6 in EECs-healthy (p < 0.05). In EECs-endo, either Pam3Csk4 or Poly I:C significantly induced CXCL10 (p < 0.05), whereas no significant response was observed after stimulation with LPS. Neither LPS, Poly I:C, nor Pam3Csk4 significantly induced IL-6 secretion in EECs-endo. Secretion of CXCL10 in EECs-healthy after stimulation with LPS was significantly higher (p < 0.05) than that in EECs-endo. CXCL10 decreased cell proliferation of EECs from both groups. Activation of nuclear factor kappa light chain enhancer of activated B cells and signal transducer and activator of transcription 3 signalings was not impaired, but activation of p38 mitogen-activated protein kinases signaling by LPS stimulation was impaired in EECs-endo. The present findings suggested that an insufficient response of EECs to a TLR4 ligand may be involved in molecular mechanisms of endometriosis-associated infertility.

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). 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 3ßHSD2 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.