FP22-5 Melatonin Modulates Mast Cell Oxidative State in the Human Testis

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP22-Testis Biology
Sunday, June 16, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 11:05 AM
Room 104 (Moscone Center)

Poster Board SUN-532
Soledad P Rossi1, Stefanie Windschuettl2, Maria E Matzkin1, Claudio Terradas3, Roberto Ponzio4, Elisa Puigdomenech5, Oscar Levalle3, Ricardo S Calandra*1, Artur Mayerhofer2 and Monica B Frungieri1
1Institute of Biology and Experimental Medicine (IBYME-CONICET), Buenos Aires, Argentina, 2Anatomy and Cell Biology, Munich, Germany, 3Durand Hospital, Buenos Aires, Argentina, 4School of Medicine, Buenos Aires, Argentina, 5Medical Institute PREFER, Buenos Aires, Argentina
We have recently demonstrated the existence of melatonin in Syrian hamster testes and its regulatory action on androgen production (1,2). Melatonin may also be a regulator of the oxidative state of cells. Hence, we now turned to the human and investigated the presence of melatonin in testicular biopsies and its potential effect on the oxidative state of gonadal mast cells (MCs). Biopsies from patients suffering hypospermatogenesis (H) or Sertoli cell only (SCO) syndrome were used. Melatonin testicular concentrations were determined by ELISA. No significant differences were found between H biopsies (12.30 ± 2.87 fmol/g tissue) and SCO biopsies (9.39 ± 0.65 fmol/g tissue). However, melatonin concentrations in testes showed a direct positive correlation with the testicular expression of the antioxidant enzymes catalase (R= 0.732, p<0.05), superoxide dismutase 1 (SOD1) (R= 0.837, p<0.05) and peroxiredoxin 1 (R= 0.791, p< 0.05).

We have previously shown that MCs are significantly increased in testes of infertile men (3). Now, by laser capture microdissection technique and PCR, we detected the expression of the mel1a receptor and antioxidant enzymes in testicular MCs.

Physiological studies cannot be performed on human testicular biopsies and human testicular MC lines are not available. Therefore, non-testicular human HMC-1 MCs which express mel1a receptors were used to further characterize the interactions between melatonin and the intracellular redox state.

Incubation of MCs in the presence of H202 (10-4 M) significantly induced the expression of catalase and SOD1 evaluated by real-time PCR and/or Western blot, and the generation of reactive oxygen species (ROS) determined by fluorescence. A 10-7M dose of melatonin further increased the expression of catalase, SOD1 and peroxiredoxin 1 and generated lower levels of ROS than H2O2 alone. In contrast, a 10-5M concentration of melatonin increased SOD1 expression but did not affect catalase and peroxiredoxin 1 expression. Unexpectedly, 10-5M melatonin generated higher levels of ROS than H2O2alone.

Taking together, the findings indicate that melatonin is a potential modulator of the testicular oxidative state by acting at least on the local MC population. Moreover, melatonin shows a dual effect on MC redox state being antioxidant at low levels but prooxidant at high concentrations.

(1) Frungieri MB et al., Endocrinology 2005; 146:1541. (2) Rossi SP et al., Gen Comp Endocrinol 2012; 178:153. (3) Meineke V et al., Fertil Steril 2000; 74:239.

Nothing to Disclose: SPR, SW, MEM, CT, RP, EP, OL, RSC, AM, MBF

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Sources of Research Support: Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT), Fundación Roemmers, Ministerio de Ciencia, Tecnología e Innovación Productiva (MINCyT) of Argentina and Deutscher Akademischer Austausch Dienst (DAAD) and Deutsche Forschungsgemeinschaft (DFG) of Germany.