HSP90 Antibodies: A Detrimental Factor Responsible for Ovarian Dysfunction

Abstract

Earlier studies from our group have established that about 47% cases of autoimmune ovarian failure are due to presence of autoantibodies to Heat Shock Protein 90 (HSP90). However, there are no reports correlating pathological effects of HSP90 autoantibodies leading to ovarian failure. Antibodies to HSP90 in female mouse model were generated by active immunization with an immunodominant peptide of HSP90, followed by detailed analysis of several reproductive parameters. Estrous cyclicity remains unchanged; however, there was a significant drop in the fertility index due to an increase in pre- and post-implantation loss, associated with an increased incidence of degenerated eggs and embryos. The ovaries showed an increase in the number of empty and degenerated follicles and extensive granulosa cell deaths, which was reflected by the decrease in the levels of Nobox and Gja1 gene expression. This study underlines a critical role played by HSP90 in ovarian folliculogenesis and highlights the implications of the presence of anti-HSP90 antibodies in infertile women.