Endocrine Abstracts (2011) 26 P142

P450 aromatase over-expressing mice (AROM+) as a model for infertility in men

L Strauss1,2, M Adam3, A Mayerhofer1 & M Poutanen1,2

1Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland; 2Turku Center for Disease Modeling, University of Turku, Turku, Finland; 3Anatomy and Cell Biology, Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-University Munich, Munich, Germany.

AROM+ mice express universally the human P450 aromatase enzyme, leading to increased serum and intratesticular E2/T ratio. AROM+ mice are infertile and present with testicular inflammation characterized by a high amount of macrophages, mast cells and fibrosis. Interestingly, testis macrophage and mast cell infiltration together with fibrosis has also been connected to infertility in men. The aim of the study was to find out whether there are similar changes at the molecular level in the testes of AROM+ mice and infertile men having testicular fibrosis. Illumina gene expression array was carried out in AROM+ testes and testes of infertile men having fibrosis, and wild type mice or fertile men were used as controls, respectively. Immunohistochemical and qRT-PCR analyses were further performed to confirm findings in the array, and human peritubular cell culture was used for functional studies. The most interested finding was that decorin, an extracellular proteoglycan, was up-regulated in AROM+ testis and in the testis of infertile men as compared with the respective controls. Decorin expression was localized to the extracellular matrix of the interstitial tissue both in AROM+ and infertile human testis. Functional studies with human peritubular cells further showed that decorin blocks growth factor -induced proliferation and differentiation of peritubular cells. Increased decorin is, thus, disturbing paracrine signaling pathways in the human testis. AROM+ mouse serves as a model for studying infertility associated with testicular fibrosis in men. Further studies are needed to define the mechanism by which the hormonal imbalance, especially the increased testicular E2/T ratio, brings about chronic inflammation and fibrosis in the human testis.

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