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Hum. Reprod. Advance Access published online on June 2, 2009
Human Reproduction, doi:10.1093/humrep/dep200
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© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed: the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given: if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative word this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Effect of fetal or neonatal exposure to monobutyl phthalate (MBP) on testicular development and function in the marmoset

Chris McKinnell1,3, Rod T. Mitchell1, Marion Walker1, Keith Morris1, Chris J.H. Kelnar2, W Hamish Wallace2 and Richard M. Sharpe1

1 MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK 2 Edinburgh Royal Hospital for Sick Children, 9 Sciennes Road, Edinburgh EH9 1LF, UK

3 Correspondence address. Tel: +44-131-242-9113; Fax: +44-131-242-6231; E-mail: c.mckinnell{at}hrsu.mrc.ac.uk

BACKGROUND: Fetal exposure of male rats to some phthalates induces reproductive abnormalities, raising concerns for similar effects in humans. In order to address this in a more appropriate animal model, the aim of the present studies was to investigate the effect of fetal/neonatal exposure to monobutyl phthalate (MBP) in a non-human primate, the marmoset. In particular, to determine if exposure resulted in effects at birth, or in adulthood, similar to those in male rats, and whether there was evidence for induction of carcinoma-in-situ (CIS) or testicular germ cell tumours (TGCT).

METHODS: Pregnant female marmosets were dosed from ~7–15 weeks gestation with 500 mg/kg/day MBP and male offspring studied at birth (1–5 days; n = 6) or in adulthood (n = 5). In another study, newborn males (n = 5 co-twins) were dosed with 500 mg/kg/day MBP for 14 days, commencing at ~4 days of age.

RESULTS: Fetal exposure of marmosets to MBP did not affect gross testicular morphology, reproductive tract development or testosterone levels at birth, nor were germ cell number and proliferation, Sertoli cell number or germ:Sertoli cell ratio affected. In two of six MBP-exposed animals, unusual clusters of undifferentiated germ cells were found, but their significance is unclear. Neonatal MBP treatment did not affect germ cell numbers or differentiation. Fetal exposure to MBP did not affect testis size/morphology, germ cell numbers or fertility in adulthood. There was no evidence for CIS or TGCT.

CONCLUSIONS: Fetal exposure of marmosets to MBP does not measurably affect testis development/function or cause testicular dysgenesis, and no effects emerge by adulthood. Some effects on germ cell development were found, but these were inconsistent and of uncertain significance.

Key words: fetal/germ cells/monobutyl phthalate/neonatal/testis

Submitted on March 5, 2009; resubmitted on April 27, 2009; accepted on May 6, 2009.


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