Metabolomics in the assessment of chemical-induced reproductive and developmental outcomes using non-invasive biological fluids: application to the study of butylbenzyl phthalate.
This study was conducted to evaluate the use of metabolomics for improving our ability to draw correlations between early life exposures and reproductive and/or developmental outcomes. Pregnant CD rats were exposed by gavage daily during gestation to vehicle or to butylbenzyl phthalate (BBP) in vehicle at a level known to induce effects in the offspring and at a level previously not shown to induce effects. Urine was collected for 24 h (on dry ice using all glass metabolism chambers) from dams on gestational day 18 (during exposure) and on post natal day (pnd) 21, and from pnd 25 pups. Traditional phenotypic anchors were measured in pups (between pnd 0 and pnd 26). Metabolomics of urine collected from dams exposed to vehicle or BBP exhibited different patterns for endogenous metabolites. Even three weeks after gestational exposure, metabolic profiles of endogenous compounds in urine could differentiate dams that received the vehicle, low dose or high dose of BBP. Metabolic profiles could differentiate male from female pups, pups born to dams receiving the vehicle, low or high BBP dose, and pups with observable adverse reproductive effects from pups with no observed effects. Metabolites significant to the separation of dose groups and their relationship with effects measured in the study were mapped to biochemical pathways for determining mechanistic relevance. The application of metabolomics to understanding the mechanistic link between low levels of environmental exposure and disease/dysfunction holds huge promise, because this technology is ideal for the analysis of biological fluids in human populations.
Sumner
Susan
S
Health Sciences, RTI International, 3040 Cornwallis Drive, Research Triangle Park, NC 27709, USA. ssumner@rti.org
Snyder
Rodney
R
Burgess
Jason
J
Myers
Christina
C
Tyl
Rochelle
R
Sloan
Carol
C
Fennell
Timothy
T
D000014:Abnormalities, Drug-Induced; D000818:Animals; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018811:Maternal Exposure; D055432:Metabolomics / Q000379:methods*; D010795:Phthalic Acids / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D012727:Sex Characteristics; D013223:Statistics as Topic; D014556:Urine / Q000737:chemistry*
D052244:Endocrine Disruptors; D010795:Phthalic Acids; C027561:butylbenzyl phthalate