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Flow cytometric assessment of trophosphamide toxicity on mouse spermatogenesis

Flow cytometric assessment of trophosphamide toxicity on mouse spermatogenesis The effects of trophosphamide on mouse reproductive cells have been investigated by flow cytometric analysis of testicular cell populations and alterations of sperm chromatin structure. Mice were treated with single intraperitoneal injections of TP, the doses ranging between 50 and 150 mg/kg, and were killed after 7, 14, 21, 28, 35, or 49 days. Dose‐dependent reductions of tetraploid cells, round spermatids, and elongated spermatids were detected at 7, 21, and 28 days, respectively, reflecting cytotoxic damage to the differentiating spermatogonia compartment. The dose necessary to reduce the number of differentiating spermatogonia to half the control value was ∼ 70 mg/kg. Stem cells were not affected by this treatment, and the normal spermatogenic process was restored after 7 weeks. In addition, cauda epididymal sperm were analyzed by the sperm chromatin structure assay, a flow cytometric measurement of the susceptibility of the sperm nuclear DNA to in situ acid denaturation; a statistically significant increase of sperm with altered chromatin structure was detected after a TP treatment of 150 mg/kg. Together with previous findings published in the literature, where the same doses induced heritable genetic damage, this study demonstrates a marked adverse cytotoxic effect of TP on the male reproductive integrity. All this information should be taken into consideration when TP is used in chemotherapeutic regimens. © 1996 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cytometry Wiley

Flow cytometric assessment of trophosphamide toxicity on mouse spermatogenesis

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Publisher
Wiley
Copyright
Copyright © 1996 Wiley‐Liss, Inc., A Wiley Company
ISSN
0196-4763
eISSN
1097-0320
DOI
10.1002/(SICI)1097-0320(19960601)24:2<174::AID-CYTO10>3.3.CO;2-S
Publisher site
See Article on Publisher Site

Abstract

The effects of trophosphamide on mouse reproductive cells have been investigated by flow cytometric analysis of testicular cell populations and alterations of sperm chromatin structure. Mice were treated with single intraperitoneal injections of TP, the doses ranging between 50 and 150 mg/kg, and were killed after 7, 14, 21, 28, 35, or 49 days. Dose‐dependent reductions of tetraploid cells, round spermatids, and elongated spermatids were detected at 7, 21, and 28 days, respectively, reflecting cytotoxic damage to the differentiating spermatogonia compartment. The dose necessary to reduce the number of differentiating spermatogonia to half the control value was ∼ 70 mg/kg. Stem cells were not affected by this treatment, and the normal spermatogenic process was restored after 7 weeks. In addition, cauda epididymal sperm were analyzed by the sperm chromatin structure assay, a flow cytometric measurement of the susceptibility of the sperm nuclear DNA to in situ acid denaturation; a statistically significant increase of sperm with altered chromatin structure was detected after a TP treatment of 150 mg/kg. Together with previous findings published in the literature, where the same doses induced heritable genetic damage, this study demonstrates a marked adverse cytotoxic effect of TP on the male reproductive integrity. All this information should be taken into consideration when TP is used in chemotherapeutic regimens. © 1996 Wiley‐Liss, Inc.

Journal

Cytometry – Wiley

Published: Jun 1, 1996

Keywords: Trophosphamide; reproductive toxicology; spermatogenesis; flow cytometry; sperm chromatin structure

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