This study aimed to analyse global metabolomic changes associated with
trans-resveratrol (RSV) treatment in mice with
cryptorchidism using untargeted metabolomics.
Cryptorchidism was established surgically in Kunming mice, which were then treated with 20µg g-1 day-1, s.c., RSV for 35 consecutive days. Typical manifestations of
spermatogenesis arrest were seen in mice with
cryptorchidism, and RSV treatment for 35 days restored spermatogenesis. Liquid chromatography-tandem mass spectrometry was used to profile the metabolome of testes from mice in the control (non-cryptorchid, untreated), cryptorchid and RSV-treated cryptorchid groups. In all, 1386 and 179 differential metabolites were detected in the positive and negative modes respectively. Seven and six potential
biomarkers were screened for
spermatogenesis arrest and restoration respectively. Pathway analysis showed changes in 197 metabolic pathways. The
hexosamine biosynthesis pathway was inhibited in the cryptorchid group, which probably resulted in a decrease in the end product,
uridine diphosphate N-acetylglucosamine (
UDP-GlcNAc). Immunoblot analysis showed that total testicular
protein O-linked β-
N-acetylglucosamine glycosylation was related to
spermatogenesis arrest, further indicating a decrease in
UDP-GlcNAc in the cryptorchid group. Thus, untargeted metabolomics revealed the biochemical pathways associated with the restoration of metabolic status in the cryptorchid group following RSV treatment and the findings could be used to monitor the response to RSV treatment. This study provides a meaningful foundation for the future clinical application of RSV in the treatment of spermatogenesis dysfunction.