Hum. Reprod. Advance Access originally published online on September 11, 2007
Human Reproduction 2007 22(11):2919-2927; doi:10.1093/humrep/dem256
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Human fetal testis Leydig cell disruption by exposure to the pesticide dieldrin at low concentrations
1 Department of Obstetrics and Gynaecology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK 2 Department of Medical Genetics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK 3 Medical Microbiology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK 4 School of Biological and Molecular Sciences, Oxford Brookes University, Oxford OX3 0BP, UK 5 Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA 02111, USA 6 School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire LE12 5RD, UK
7 Correspondence address. Tel: +44-1224-552633; Fax: +44-1224-684880; E-mail: p.a.fowler{at}abdn.ac.uk
BACKGROUND: Declining human reproductive health over the last 60 years has been proposed to be due to effects of environmental chemicals, especially endocrine disrupting compounds, on fetal development. We investigated whether a model pesticide, dieldrin, at concentrations within both maternal circulation and environmental ranges (1 pmol/l = 0.0004 p.p.b. = 380.9 pg/l), could disrupt the human fetal testis.
METHODS: Human fetal testes were collected during the second trimester, a critical period of male sexual differentiation (development and masculinization). Testis explants were cultured for 24 h in the presence and absence of LH (10–1000 IU LH/l) and dieldrin (1 pmol and 1 nmol/l). Endocrine, immunohistological and proteome characteristics of the tissues were investigated.
RESULTS: Exposure to dieldrin reduced LH-induced testosterone secretion (P < 0.05) and tissue protein concentrations of LH receptor and steroid acute regulatory protein (P < 0.05). Dieldrin altered proteins associated with cancer, apoptosis, transcription and development. Wnt-2b was reduced 3-fold and immunolocalized to Leydig and Sertoli cells. Dieldrin also reversed some LH-induced changes in protein expression, supporting the conclusion that Leydig cell function is at risk from environmental chemicals.
CONCLUSIONS: Our findings indicate that exposure to very low, biologically relevant, concentrations of environmental chemicals could affect the fetal human Leydig cell, reducing testosterone secretion and potentially leading to subtle dysregulation of reproductive development and adult fecundity.
Key words: human/fetal/testis/pesticide/endocrine disruption
Submitted on May 25, 2007; resubmitted on June 28, 2007; accepted on July 11, 2007.
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