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Adenosine accumulation causes metabolic disorders in testes and associates with lower testosterone level in obese

Xiao Yang1, Yang Zhao1, Qi Sun1

  • 1Center for Molecular Metabolism, Nanjing University of Science and Technology, Nanjing, China.

Molecular Reproduction and Development
|February 7, 2020
PubMed

Insights

Obesity in men leads to testicular adenosine accumulation, disrupting steroid metabolism and lowering testosterone levels. This impacts male fertility by causing metabolic disorders in the testes.

Area of Science:

  • Reproductive Biology
  • Metabolic Disorders
  • Obesity Research

Background:

  • Obesity and type 2 diabetes are linked to male subfertility and infertility.
  • Nutritional status and obesity-related signals' impact on fertility is understudied.
  • Previous work linked 5'-adenosine monophosphate (5'-AMP) elevation and adenosine accumulation to insulin resistance in obese mice.

Purpose of the Study:

  • To investigate the role of adenosine accumulation in testicular function in obese mice.
  • To explore the molecular mechanisms linking obesity, adenosine, and reduced testosterone levels.

Main Methods:

  • Messenger RNA sequencing to analyze gene expression changes in testes.
  • Metabolomic analysis using 1H nuclear magnetic resonance (NMR) to compare testicular metabolic profiles.
  • Western blotting to assess key signaling pathways (AKT, mTOR) and cell proliferation (PCNA).

Main Results:

  • Adenosine accumulation in the testis is a common marker in both genetic and diet-induced obese mice.
  • Gene expression analysis revealed overlapping changes in steroid metabolism and hormone regulation pathways.
  • Reduced serum testosterone levels were observed in obese mice models.
  • 5'-AMP treatment inhibited AKT/mTOR signaling and reduced proliferating cell nuclear antigen (PCNA) expression in testes.

Conclusions:

  • Testicular adenosine accumulation, driven by obesity, causes metabolic dysfunction.
  • This metabolic disruption is associated with decreased testosterone levels and potentially impaired male fertility.
  • Adenosine accumulation may be a key factor contributing to male infertility in obese individuals.
Keywords:
adenosinemRNA sequencingmetabolomicsobesityreproduction

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