Effect of fetal or neonatal exposure to monobutyl phthalate (MBP) on testicular development and function in the marmoset.
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 approximately 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 approximately 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.
McKinnell
Chris
C
MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. c.mckinnell@hrsu.mrc.ac.uk
Mitchell
Rod T
RT
Walker
Marion
M
Morris
Keith
K
Kelnar
Chris J H
CJ
Wallace
W Hamish
WH
Sharpe
Richard M
RM
D000818:Animals; D000831:Animals, Newborn; D002144:Callithrix; D005260:Female; D005854:Germ Cells / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure; D010795:Phthalic Acids / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*; D012708:Sertoli Cells / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000254:growth & development*
D010795:Phthalic Acids; C028577:monobutyl phthalate