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Abstract

Volume 15, Issue 2 (March 2013) 15, 261–268; 10.1038/aja.2012.138

Brief maternal exposure of rats to the xenobiotics dibutyl phthalate or diethylstilbestrol alters adult-type Leydig cell development in male offspring

Richard Ivell1,2, Kee Heng1, Helen Nicholson3 and Ravinder Anand-Ivell2,4

1 School of Molecular and Biomedical Science, University of Adelaide, Adelaide 5005, Australia
2 FBN Leibniz Institute of Farm Animal Biology, Dummerstorf 18196, Germany
3 Centre for Reproduction and Genomics, Otago School of Medical Sciences, University of Otago, Dunedin 9054, New Zealand
4 School of Pharmacy and Medical Sciences, University of South Australia, Adelaide 5000, Austra

Correspondence: Dr R Anand-Ivell, (anand-ivell@fbn-dummerstorf.de)

Received 21 September 2012; Revised 22 October 2012; Accepted 25 October 2012

Abstract

Maternal exposure to estrogenic xenobiotics or phthalates has been implicated in the distortion of early male reproductive development, referred to in humans as the testicular dysgenesis syndrome. It is not known, however, whether such early gestational and/or lactational exposure can influence the later adult-type Leydig cell phenotype. In this study, Sprague–Dawley rats were exposed to dibutyl phthalate (DBP; from gestational day (GD) 14.5 to postnatal day (PND) 6) or diethylstilbestrol (DES; from GD14.5 to GD16.5) during a short gestational/lactational window, and male offspring subsequently analysed for various postnatal testicular parameters. All offspring remained in good health throughout the study. Maternal xenobiotic treatment appeared to modify specific Leydig cell gene expression in male offspring, particularly during the dynamic phase of mid-puberty, with serum INSL3 concentrations showing that these compounds led to a faster attainment of peak values, and a modest acceleration of the pubertal trajectory. Part of this effect appeared to be due to a treatment-specific impact on Leydig cell proliferation during puberty for both xenobiotics. Taken together, these results support the notion that maternal exposure to certain xenobiotics can also influence the development of the adult-type Leydig cell population, possibly through an effect on the Leydig stem cell population.

Keywords: diethylstilbestrol (DES); INSL3; Leydig cells; dibutyl phthalate (DBP); puberty; testis

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