ACCUMULATION OF CLUSTERIN SULFATED GLYCOPROTEIN-2 IN DEGENERATING PACHYTENE SPERMATOCYTES OF ADULT RATS TREATED WITH METHOXYACETIC ACID

Clusterin is a ubiquitous glycoprotein that is produced constitutively by Sertoli cells at relatively high amounts. Its association with apo ptosis, damage, disease, and repair in nongonadal tissues led us to in vestigate whether clusterin could be part of a damage-induced response in Sertoli cells brought on by apoptosis of an adjacent cell type. Th erefore, the objective of this study was to treat adult rats with meth oxyacetic acid (MAA) to selectively destroy pachytene spermatocytes, e xamine the localization and expression of testicular clusterin, and re late this to the timing of DNA fragmentation, a hallmark of apoptosis. Clusterin protein was localized to the cytoplasm of pachytene spermat ocytes at 6 h post-MAA, whereas clusterin mRNA was localized to Sertol i cells. Morphological degeneration of dying cells and DNA fragmentati on were not seen until 12 h. Thus, Sertoli cell-derived clusterin had accumulated in the cytoplasm of degenerating spermatocytes early in th e apoptotic process. On the basis of these results and the known bindi ng of clusterin to hydrophobic macromolecules, we hypothesize that clu sterin is produced by Sertoli cells as a mechanism to ''clear'' potent ially harmful cellular components during the degeneration of germ cell s and remodeling of their membranes that occur normally during spermat ogenesis.