Toxicant-induced leakage of germ cell-specific proteins from seminiferous tubules in the rat: relationship to blood-testis barrier integrity and prospects for biomonitoring.

Toxicological Sciences : an Official Journal of the Society of Toxicology
Naomi D ElkinRichard M Sharpe

Abstract

Evaluation of testicular toxicity during drug development is currently based on histopathological evaluation. A sensitive biomarker for testicular toxicology could provide an in-life and "early warning" measurement. Previous studies suggested that disruption of spermatogenesis induced leakage of germ cell proteins from seminiferous tubules (STs) into interstitial fluid (IF); such proteins have potential for use as biomarkers. To investigate this possibility further, adult male rats were treated with three testicular toxicants thought to have differing sites of action; cadmium chloride affects the blood-testis barrier (BTB), methoxyacetic acid (MAA) disrupts pachytene spermatocytes, and 1,3-dinitrobenzene (DNB) targets Sertoli cells. IF proteins were assessed by Coomassie-based dye-stained gels. Immunostaining was used to identify toxicant-induced damage (DAZL) and BTB integrity (ZO-1, occludin, N-cadherin, and β-catenin) and function (biotin). Cadmium chloride induced dose-dependent leakage of proteins from STs into IF coincident with loss of integrity and function of the BTB. Two of the "leaked" proteins were identified on Westerns as being germ cell specific, namely VASA and fatty acid-binding protein 9 (FABP9). In contrast, ...Continue Reading

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Citations

Jan 5, 2013·Human Reproduction Update·Xiang XiaoC Yan Cheng
Nov 1, 2011·Pharmacological Reviews·C Yan Cheng, Dolores D Mruk
Sep 15, 2012·Journal of Cell Science·Xiang XiaoDolores D Mruk
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Jun 9, 2020·Molecular Reproduction and Development·Jungbin Yoon, Kunsoo Rhee
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Feb 28, 2021·Molecular and Cellular Endocrinology·Rashid A Aldahhan, Peter G Stanton

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Methods Mentioned

BETA
electrophoresis
Assay
Infrared Imaging

Software Mentioned

ImageQuant
ImageMaster 2D Platinum
GraphPad Prism
Odyssey
Zen

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