: EXPRESSION OF THE IGF SYSTEM IN GERM CELLS OF THE IMMATURE HUMAN TESTIS. POSSIBLE ROLE IN THE PRESERVATION OF THE GERM CELL POOL

ESPERANZA BERENSZTEIN; FLORENCIA CAYROL; MARIA S. BAQUEDANO; CAROLINA PEPE; NORA SARACO; PABLO CUBILLANA; PABLO VARELA; MARIA T. DE DAVILA; MARCO A. RIVAROLA; ALICIA BELGOROSKY

Washington DC

Congreso; Annual Meeting of The Endocrine Society; 2009

A complex network of signs is involved in the regulation of immature germ cells (IGC) pool preservation before puberty. The mechanisms that might participate are unknown. In previous studies we have shown that aromatase (ARO) and estrogen receptor beta are expressed in IGCs from prepubertal human testis (HT). We have also described that ARO expression changes with age, being higher in HT from neonatal (NEO) and postnatal activation (PNA) periods than during prepuberty (PP) (Berensztein, Ped Res 2006). The subject of our current investigation focuses on the expression of IGFs system and insulin receptor (IR) as possible players in the IGC pool regulation. HT (n = 36) were divided in 3 age groups (Gr): Gr1 NEO (< 1 mo), Gr2 PNA (17mo), Gr3 PP (early and late PP). The relative proportion of each type of germ cell (GC), gonocyte or spermatogonia, in the different age groups was analyzed. Immunoexpression of OCT3/4 (marker of fetal GC), c-kit (marker of IGC), MAGE-A4 (marker of spermatogonia), IGF1, IGF2, type 1 IGF receptor (IGFR1) and IR in GC was studied. Data were expressed as % of positive GC, mean SD. We found that gonocyte number decreases after the neonatal period (Gr1, 20.9 3.8%; Gr2, 8.9 4.3%; Gr 3, 3.5 2.3 %). OCT3/4 expression was not detected in any  age group. In the case of C-kit, the highest expression was observed in Gr1, followed by Gr2 and the least by Gr3 (41.7 14.3, 24.4 17.3, 14.5 13.2, p < 0.05). These results indicate that C-kit expression decreases significantly with age (r = -0.458, p = 0.021). MAGE-A4, only determined in Gr2 and Gr3, was 27.2 and 31.7 %, respectively. High expression of IGF2 (25.6 3.1, 29.2 7.1 and 28.3 9.6) and IR (37.3 11.9, 41.4 11.3 and 50.8 6.5) was found, while moderate expression of IGF1 (11.7 8.82, 7.28 7.06 and 6.98 4.57) and IGFR1 (7.7 5.5, 9.6 7.5, and 6.15 7.85, Gr1, Gr2 and Gr3 respectively) was also observed. The absence of OCT3/4 expression suggests that this marker is not expressed in normal postnatal GC. The decreasement in c-kit expression with age suggests that there are changes in the GC population in HT during PP. Since the percentage of IGF1, IGF2, IGFR and IR expression in GC does not change as a function of age, as well as that of MAGE-A4, it can be proposed that the IGFs system and insulin might have a role in maintaining an adequate GC pool, mainly spermatogonia, in the prepubertal HT