Abstract

Administration of dibutyl phthalate (DBP) to pregnant rats causes reproductive disorders in male offspring, resulting from suppression of intratesticular testosterone, and is used as a model for human testicular dysgenesis syndrome (TDS). DBP exposure in pregnancy induces focal dysgenetic areas in fetal testes that appear between e19.5–e21.5, manifesting as focal aggregation of Leydig cells and ectopic Sertoli cells (SC). Our aim was to identify the origins of the ectopic SC. Time-mated female rats were administered 750 mg/kg/day DBP in three different time windows: full window (FW; e13.5–e20.5), masculinisation programming window (MPW; e15.5–e18.5), late window (LW; e19.5–e20.5). We show that DBP-MPW treatment produces more extensive and severe dysgenetic areas, with more ectopic SC and germ cells (GC) than DBP-FW treatment; DBP-LW induces no dysgenesis. Our findings demonstrate that ectopic SC do not differentiate de novo, but result from rupture of normally formed seminiferous cords beyond e20.5. The more severe testis dysgenesis in DBP-MPW animals may result from the presence of basally migrating GC and a weakened basal lamina, whereas GC migration was minimal in DBP-FW animals. Our findings provide the first evidence for how testicular dysgenesis can result after normal testis differentiation/development and may be relevant to understanding TDS in human patients.

Details

Title
Dibutyl phthalate induced testicular dysgenesis originates after seminiferous cord formation in rats
Author
Lara, Nathália L M 1 ; Sander van den Driesche 2 ; Macpherson, Sheila 3 ; França, Luiz R 4 ; Sharpe, Richard M 3 

 MRC Centre for Reproductive Health, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK; Laboratory of Cellular Biology, Department of Morphology, Federal University of Minas Gerais, Belo Horizonte/MG, Brazil 
 MRC Centre for Reproductive Health, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK; Centre for Integrative Physiology, Biomedical Sciences, Hugh Robson Building, University of Edinburgh, Edinburgh, UK 
 MRC Centre for Reproductive Health, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK 
 Laboratory of Cellular Biology, Department of Morphology, Federal University of Minas Gerais, Belo Horizonte/MG, Brazil; National Institute for Amazonian Research, Manaus/AM, Brazil 
Pages
1-13
Publication year
2017
Publication date
May 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1955673992
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.