PMID- 8607140 OWN - NLM STAT- MEDLINE DCOM- 19960517 LR - 20220318 IS - 0041-008X (Print) IS - 0041-008X (Linking) VI - 137 IP - 1 DP - 1996 Mar TI - Mono-(2-ethylhexyl) phthalate rapidly alters both Sertoli cell vimentin filaments and germ cell apoptosis in young rat testes. PG - 42-50 AB - Mono-(2-ethylhexyl) phthalate (MEHP) is a widely studied Sertoli cell toxicant. Here we describe alterations in Sertoli cell vimentin filament distribution and the incidence of testicular germ cell apoptosis in young (28-day-old) Fischer rats that were treated with MEHP (2 microgram/kg, po) and killed 0, 3, 6, or 12 hr after exposure. A collapse in vimentin filaments was observed 3 hr after MEHP exposure without accompanying changes in the pattern of Sertoli cell tubulin or actin. A progressive increase in the perinuclear condensation of the vimentin filaments was observed from 6 to 12 hr after exposure. To evaluate the consequences of these Sertoli cell changes on germ cells, the role of apoptosis in MEHP-induced testicular toxicity was examined. DNA isolated from testis of rats 6 and 12 hr after MEHP exposure showed a marked increase in low-molecular-weight DNA resulting from internucleosomal cleavage. In addition, DNA fragmentation visualized in frozen testis cross sections by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick end label (TUNEL) staining demonstrated a progressive increase in germ cell apoptosis from 6 to 12 hr after MEHP exposure. However, 3 hr after MEHP exposure, the incidence of TUNEL-positive germ cells was significantly decreased compared to that seen in controls. Taken together, the early collapse in Sertoli cell vimentin filaments and the concurrent decrease in germ cell apoptosis suggests that MEHP engenders Sertoli cell dysfunction resulting in the disruption of the physiological mechanism of germ cell apoptosis. FAU - Richburg, J H AU - Richburg JH AD - Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island 02912, USA. FAU - Boekelheide, K AU - Boekelheide K LA - eng GR - R01 ES05033/ES/NIEHS NIH HHS/United States GR - T32 ES07272/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Toxicol Appl Pharmacol JT - Toxicology and applied pharmacology JID - 0416575 RN - 0 (Vimentin) RN - C42K0PH13C (Diethylhexyl Phthalate) RN - FU2EWB60RT (mono-(2-ethylhexyl)phthalate) SB - IM MH - Animals MH - *Apoptosis MH - Cell Count MH - Diethylhexyl Phthalate/*analogs & derivatives/toxicity MH - Immunohistochemistry MH - Intermediate Filaments/chemistry/*drug effects/ultrastructure MH - Male MH - Rats MH - Rats, Inbred F344 MH - Sertoli Cells/*drug effects/ultrastructure MH - Spermatozoa/cytology/*drug effects MH - Staining and Labeling MH - Testis/drug effects/ultrastructure MH - Vimentin/*analysis EDAT- 1996/03/01 00:00 MHDA- 1996/03/01 00:01 CRDT- 1996/03/01 00:00 PHST- 1996/03/01 00:00 [pubmed] PHST- 1996/03/01 00:01 [medline] PHST- 1996/03/01 00:00 [entrez] AID - S0041-008X(96)90055-1 [pii] AID - 10.1006/taap.1996.0055 [doi] PST - ppublish SO - Toxicol Appl Pharmacol. 1996 Mar;137(1):42-50. doi: 10.1006/taap.1996.0055.