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Melatonin counteracts cadmium-induced rat testicular toxicity via the mechanistic target rapamycin (mTOR) pathway

Mariem B Rhouma1, Massimo Venditti2, Asma Haddadi1

  • 1Laboratoire LR11ES41 Génétique Biodiversité et Valorisation des Bio-ressourcés, Institut Supérieur de Biotechnologie de Monastir, Université de Monastir, Monastir, Tunisia.

Journal of Experimental Zoology. Part A, Ecological and Integrative Physiology
|March 4, 2024
PubMed

Insights

Melatonin (MLT) protects rat testes from cadmium (Cd) damage, with the mammalian target of rapamycin (mTOR) pathway playing a partial role. mTOR inhibition alone negatively impacts testicular function and sperm quality.

Area of Science:

  • Reproductive biology
  • Toxicology
  • Molecular endocrinology

Background:

  • Cadmium (Cd) exposure is known to induce testicular damage in rats.
  • Melatonin (MLT) has demonstrated protective effects against Cd-induced testicular toxicity.
  • The precise molecular mechanisms underlying MLT's protective action remain unclear.

Purpose of the Study:

  • To investigate the role of the mammalian target of rapamycin (mTOR) pathway in mediating the protective effects of MLT against Cd-induced testicular damage in rats.
  • To elucidate the molecular mechanisms by which MLT counteracts Cd toxicity in testicular tissue.

Main Methods:

  • Rats were exposed to Cadmium (Cd) and treated with Melatonin (MLT) and/or Rapamycin (Rapa), an mTOR inhibitor.
  • Assessment of testicular morphology, germ and somatic cell autophagy, serum testosterone levels, and protein expression of steroidogenesis and blood-testis barrier markers.
  • Evaluation of sperm parameters and acrosome reaction capacity.

Main Results:

  • Cd exposure induced testicular damage, while MLT exhibited protective effects.
  • Inhibition of mTOR with Rapa abolished MLT's protective effects in Cd-exposed rats, indicating partial modulation by the mTOR pathway.
  • mTOR inhibition alone led to altered testicular morphology, increased autophagy, reduced testosterone, impaired steroidogenesis and blood-testis barrier integrity, and poor sperm function.

Conclusions:

  • The mTOR pathway is partially involved in mediating the protective effects of MLT against Cd-induced testicular toxicity.
  • Melatonin (MLT) can be considered a potential supplement to enhance testicular function and improve male gamete quality in the context of Cd exposure.
  • Further research is warranted to fully delineate the molecular pathways involved in MLT's action on testicular health.
Keywords:
blood–testis barriercadmiummTOR pathwaymelatoninrapamycinspermatogenesis

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