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Inhibition of the fructose transporter Glut5 boosts androgen production by dysregulating the metabolism of murine Leydig cells

GSE294305 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2026/04/10 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 12 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
12 samples: 6 × mLTC-1 murine Leydig cell line, control, vs 6 × mLTC-1 murine Leydig cell line, 100µM MSNBA,Groups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
Over the past few decades, a significant change in global sugar intake has coincided with a rising incidence of male infertility, which is now a major public health concern. Diets rich in fructose have been implicated in both male infertility and an increased susceptibility to metabolic disorders like obesity, diabetes, and related heart problems.
Read the full summary ↓
While fructose is known to be present in seminal fluid and crucial for sperm motility, the precise role of fructose in testicular function remains largely unknown. While GLUT5 is recognized as the exclusive fructose transporter for dietary uptake, it is known to be expressed in germ and Leydig cells. Our recent study has shown that disrupting the GLUT5 gene in male mice impairs both spermatogenesis and steroidogenesis. However, its specific role within Leydig cells remained unexplored. We investigated this by inhibiting a murine Leydig cell line (mLTC-1) with MSNBA, a specific inhibitor of GLUT5. To comprehensively understand the molecular mechanisms of GLUT5 in these cells, we employed a multi-omics approach. Exposition to MNSBA reduced intracellular fructose content, limited cell proliferation and enhanced androgen production. The increased production of testosterone was linked to the upregulation of steroidogenesis-related genes such as Hsd3b, and steroidogenic acute regulatory protein (StAR). In Leydig cell, inhibition of GLUT5 modify lipid and carbohydrate metabolism. Lipidomic analysis showed a decrease in cholesterol esters and a shift in the ratio of polyunsaturated fatty acids (PUFAs) to monounsaturated fatty acids (MUFAs). These lipid changes were correlated with alterations in the expression of mRNA encoding enzymes involved in lipogenesis, such as Elovl6. Metabolomics analysis showed a reduction of different metabolite of the glycolysis except for pyruvate and lactate. However, pyruvate molecules could be produced from the higher branched-chain amino acids content. BRB-seq approach has revealed an upregulation of several androgen-sensitive genes such as lactate dehydrogenase A (Ldha) producing lactate and a down regulation of several genes associated to insulin pathway. In summary, Glut5 is involved in Leydig cells for the fructose intake. Perturbation of the Glut5 activity led to an alteration of the energy metabolism but stimulated the androgen production. Because androgens are known to influence spermatogenesis, these findings raise the importance of the fructose intake in the function of male fertility.
This dataset
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE294305_RAW.tar (it can run to tens of gigabytes).

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1248981 and SRA study SRP578106. Searching any of these in the dataset finder brings you back here.

Study design
6 × mLTC-1 murine Leydig cell line, control, vs 6 × mLTC-1 murine Leydig cell line, 100µM MSNBA,

Supports a between-group comparison across 12 samples.

How we read this: 2 replicated groups read from 12 sample titles; they account for 12 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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