Immune-mediated destruction of ovarian follicles associated with the presence of HSP90 antibodies.

SUMMARY We previously established that the presence of autoantibodies to heat-shock protein 90 (HSP90) is one common causes of female infertility, and demonstrated that its presence leads to detrimental effects on ovarian and reproductive function in mice. The pathophysiological mechanism and alteration in the immune physiology, however, remain unknown. We therefore carried out detailed analysis of various immune cells in the spleen and ovary following immunization of C57BL/6 female mice to generate antibodies to HSP90 in the general circulation. We observed a significant increase in levels of CD45− cells; CD4+ T cells; Ly6G6C+ cells; and CD11b+ Ly6G+ cells in the spleen of these mice, which correlate with the increased anti-HSP90 antibody production. Ovarian- and granulosa-cell populations also showed increased infiltration of CD45+ leukocytes and neutrophil and monocyte populations, which may have led to the observed ovarian follicular degeneration that predominantly manifested as empty follicles. A decrease in the number of functional ovarian follicles was also associated with a decrease in the level of Gdf9 gene expression. Thus, changes in the immune physiology of the spleen and ovary that leads to the generation of antibodies to HSP90 can also bring about the destruction of ovarian follicles. Mol. Reprod. Dev. 82: 81–89, 2015. © 2015 Wiley Periodicals, Inc.