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 apoptosis, damage, disease, and repair in nongonadal tissues led us to investigate whether clusterin could be part of a damage-induced response in Sertoli cells brought on by apoptosis of an adjacent cell type. Therefore, the objective of this study was to treat adult rats with methoxyacetic acid (MAA) to selectively destroy pachytene spermatocytes, examine the localization and expression of testicular clusterin, and relate this to the timing of DNA fragmentation, a hallmark of apoptosis. Clusterin protein was localized to the cytoplasm of pachytene spermatocytes at 6 h post-MAA, whereas clusterin mRNA was localized to Sertoli cells. Morphological degeneration of dying cells and DNA fragmentation were not seen until 12 h. Thus, Sertoli cell-derived clusterin had accumulated in the cytoplasm of degenerating spermatocytes early in the apoptotic process. On the basis of these results and the known binding of clusterin to hydrophobic macromolecules, we hypothesize that clusterin is produced by Sertoli cells as a mechanism to "clear" potentially harmful cellular components during the degeneration of germ cells and remodeling of their membranes that occur normally during spermatogenesis.