Sexual dimorphism in urinary metabolite profiles of Han Wistar rats revealed by nuclear-magnetic-resonance-based metabonomics.
Gender-dependent metabolic variation in Han Wistar rats (n=25 male and n=25 female) was investigated using (1)H nuclear magnetic resonance (NMR) spectroscopy of urine coupled with chemometric methods. Statistically discriminatory regions of the spectra for male and female rats were identified and biomarker characterization was achieved by the further application of solid-phase extraction chromatography with NMR detection and high-performance liquid chromatography mass spectrometry. A novel discriminating molecule was identified as the sulfate conjugate of m-hydroxyphenylpropionic acid, which was excreted in higher concentrations by male rats. Other gender-related metabolite differences in the urine profiles included higher levels of trimethylamine-N-oxide, N,N'-dimethylglycine, m-hydroxyphenylpropionic acid, N-acetylglycoprotein, and cholate in samples from female animals. These studies emphasize the utility of multicomponent metabolic profiling for investigating physiological and genetic variation in experimental animals that may be of relevance to their use as models of toxicity and disease.
Biological Chemistry, Biomedical Sciences Division, Sir Alexander Fleming Building, Imperial College, South Kensington, London SW7 2AZ, UK.
E G
EG
Stanley
N J C
NJ
Bailey
M E
ME
Bollard
J N
JN
Haselden
C J
CJ
Waterfield
E
E
Holmes
J K
JK
Nicholson
D000818:Animals; D001711:Biotransformation; D002726:Chlorogenic Acid / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003373:Coumaric Acids / Q000652:urine; D005163:Factor Analysis, Statistical; D005260:Female; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D013058:Mass Spectrometry; D008744:Methylamines / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D012521:Sarcosine / Q000031:analogs & derivatives / Q000652:urine; D012727:Sex Characteristics; D014556:Urine / Q000737:chemistry*
D003373:Coumaric Acids; D008744:Methylamines; D002726:Chlorogenic Acid; C038547:dihydro-3-coumaric acid; C025138:dimethylglycine; C005855:trimethyloxamine; D012521:Sarcosine