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Hematopoietic stem cell transplantation (HSCT) is associated with significant posttransplantation gonadotoxicity. This deficit has been mainly attributed to pretransplantation conditioning, but lower sperm counts in humans also appear to be associated with graft-versus-host disease (GVHD) following allogeneic HSCT. However, the mechanisms leading to diminished spermatocyte levels during GVHD remain unknown. Here we demonstrate that injury to intratesticular cells occurs in unconditioned F1 mice following the infiltration of donor alloreactive T cells during an acute graft-versus-host reaction (GVHR). Using computer-aided quantitative microscopic morphometry we demonstrate that the nadir of Leydig cell volume density coincides with the peak of intratesticular infiltration by donor T cells. Injury to Leydig cells correlates with an intratesticular inflammatory response characterized by interferon-gamma and tumor necrosis factor-alpha production. These results demonstrate impairment of testosterone-producing Leydig cells during a local alloresponse, thus representing a mechanism that contributes to gonadal insufficiency following allogeneic HSCT.

Original publication

DOI

10.1182/blood-2004-07-2646

Type

Journal article

Journal

Blood

Publication Date

01/04/2005

Volume

105

Pages

2988 - 2990

Keywords

Acute Disease, Animals, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Hypogonadism, Leydig Cells, Male, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Spermatogenesis, T-Lymphocytes, Testosterone