Metabolomics analysis reveals metabolic changes associated with trans-resveratrol treatment in experimental cryptorchidism mice
Siqiang Li
A * , Yun Li A B * , Fujia Chen A , Yurong Yang A , Li Song A , Chaoying Liu A B , Baogen Wang A , Yuanhong Xu A , Mingguang Shao A and Enzhong Li A C
+ Author Affiliations
- Author Affiliations
A School of Biological and Food Processing Engineering, Huanghuai University, Zhumadian, China.
B Zhumadian Academy of Industry Innovation and Development, Huanghuai University, Zhumadian, China.
C Corresponding author. Email: enzhongli@163.com
Reproduction, Fertility and Development 33(5) 328-337 https://doi.org/10.1071/RD20189
Submitted: 20 July 2020 Accepted: 11 December 2020 Published: 19 February 2021
Abstract
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 20 µg 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.
Keywords: cryptorchid mice, non-targeted metabolomics, O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation), spermatogenesis, trans-resveratrol.
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