Geldanamycin administration reduces the amount of primordial germ cells in the mouse embryo

Abstract

Heat shock proteins (HSPs) are expressed or overexpressed in response to exposure to stress. They act as molecular chaperones, ensuring the correct folding of numerous client proteins. HSP90 is one of the most conserved HSPs. Its role extends beyond stress tolerance. HSP90 also contributes to development, differenciation, apoptosis and oncogenesis. Numerous tumors are associated with an overexpression of HSP90 and this expression can be used to evaluate its metastatic capacity. Primordial germ cells (PGCs) exhibit HSP90 expression under normal conditions. PGCs arise early in development and migrate by a combination of passive and active movements towards the gonads. The aim of this work was to study the impact of an inhibition of HSP90 on the migration of the PGCs. Geldanamycin, a well established HSP90 inhibitor with potent antitumor properties was used to achieve this inhibition. 5mg of Geldanamycin were administered to E8 pregnant mice. E17 embryos were removed and fixed for staining and Immunohistochemistry with anti-HSP90 and anti-VASA antibodies. Geldanamycin-treated mouse embryos exhibited less VASA-immunopositive cells compared to the non-treated ones. These results suggest that geldanamycin administration at the time of PGCs migration reduces the number of PGCs in the gonads. HSP90 and VASA stainings were identical. We therefore expressed the idea that HSP90 could be used as a reliable marker for PGCs.