UNDIFFERENTIATED SPERMATOGONIA CELL CYCLE ARREST CONTRIBUTES TO THE IMPAIRMENT OF SPERMATOGENESIS IN THE TESTIS UNDER A CHRONIC INFLAMMATORY PROCESS

FERREIRO, EUGENIA; LUSTIG, LIVIA; MENDEZ, CINTHIA SOLEDAD; SOBARZO, CRISTIAN; THEAS, MARÍA SUSANA; GONZÁLEZ, LUCAS; JACOBO PATRICIA

Obidos

Workshop; 20th European Testis Workshop (European Workshop on the Molecular and Cellular Endocrinology of the Testis); 2018

Infertility is a main worldwide problem that affects one of six couples at reproductive age around world being the male factor responsible of 60% for the consults for infertility. Inflammation involving the presence of interstitial cell infiltrates in the testis (orchitis) or in the testis and epididymis (orchi-epididymitis) generally associated with damage of seminiferous tubules (ST) occurs in approximately 15% of patients with male infertility. We developed and experimental model of autoimmune orquitis (EAO) useful to understand the mechanisms underlying spermatogenesis disruption. EAO is characterized by an interstitial lymphomonocyte cell infiltrate, moderate in focal phase and abundant in severe EAO, increased levels of nitric oxide (NO) and TNFα, apoptosis of post-meiotic germ cells (GC) and reduced proliferation of pre-meiotic GC (spermatogonia, EP, and preleptotene spermatocytes). We hypothesize that cell cycle of CD9+ undifferentiated EP is arrested and that NO and TNFα are involved in this event. Objective: Analyze the cell cycle of CD9+undifferentiated EP and evaluate if NO and TNFα are able to regulate cell cycle progression. Conclusion: In focal EAO, CD9+ undifferentiated EP cell cycle is unaffected, however in severe EAO CD9+ EP cell cycle is arrested at G2/M phase, event that might be responsible for the decreased number of proliferating pre-meiotic germ cells previously observed in this model. The chronically exposition of EP to NO could induce arrest of these cells in orchitis, thus contributing to spermatogenesis impairment an infertility