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Real Time Analysis of Metabolic Profile in Ex Vivo Mouse Intestinal Crypt Organoid Cultures
Published on: November 3, 2014
Metabolomics analysis reveals metabolic changes associated with trans-resveratrol treatment in experimental
Siqiang Li1, Yun Li2, Fujia Chen1
1School of Biological and Food Processing Engineering, Huanghuai University, Zhumadian, China.
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 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.
Insights
Trans-resveratrol (RSV) treatment restored spermatogenesis in mice with cryptorchidism by altering metabolic pathways. This study highlights RSV
Area of Science:
- Metabolomics
- Reproductive Biology
- Biochemistry
Background:
- Cryptorchidism, or undescended testes, is associated with spermatogenesis dysfunction.
- Trans-resveratrol (RSV) is a natural polyphenol with potential therapeutic properties.
Purpose of the Study:
- To investigate the global metabolomic changes induced by trans-resveratrol (RSV) treatment in a mouse model of cryptorchidism.
- To identify biomarkers and metabolic pathways involved in spermatogenesis restoration.
Main Methods:
- Surgical induction of cryptorchidism in Kunming mice.
- Treatment with trans-resveratrol (RSV) for 35 days.
- Untargeted metabolomics using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
- Pathway analysis and immunoblotting.
Main Results:
- RSV treatment successfully restored spermatogenesis in cryptorchid mice.
- 1386 and 179 differential metabolites were identified in positive and negative modes, respectively.
- The hexosamine biosynthesis pathway was inhibited in cryptorchid mice, leading to decreased UDP-N-acetylglucosamine (UDP-GlcNAc).
- Testicular O-linked β-N-acetylglucosamine glycosylation was linked to spermatogenesis arrest.
Conclusions:
- Untargeted metabolomics revealed key biochemical pathways affected by RSV treatment in cryptorchidism.
- RSV treatment restored metabolic status and spermatogenesis, suggesting its therapeutic potential.
- Identified biomarkers and pathways can aid in monitoring RSV treatment efficacy for male infertility.

