Oxidative stress burden inhibits spermatogenesis in adult male rats: testosterone protective effect

Area of Science:

• Reproductive Toxicology
• Endocrinology
• Pharmacology

Background:

• Methotrexate (MTX) induces testicular toxicity through oxidative stress and antiproliferative effects.
• Androgens play a role in testicular function and may offer protection against toxicity.
• Aromatase inhibitors and antioxidants are being explored for their potential protective mechanisms.

Purpose of the Study:

• To investigate the protective effects of letrozole (LET), grape seed extract (GSE), and testosterone propionate (Tp) against MTX-induced testicular toxicity in male rats.
• To evaluate the impact of these agents on oxidative stress markers, cytokines, spermatogenesis, and sperm viability.
• To elucidate the mechanisms underlying androgen-mediated protection against testicular damage.

Main Methods:

• Adult male rats were treated with LET, GSE, or Tp alone, MTX alone, or in combination with these agents.
• Testicular oxidative stress markers and pro-inflammatory cytokines (TNF-α, IL-1β) were quantified.
• Spermatogenesis and sperm viability were assessed via microscopic evaluation.

Main Results:

• LET and GSE administration prior to MTX significantly improved spermatogenesis and sperm viability.
• LET and GSE treatments reduced testicular levels of oxidative stress markers and inflammatory cytokines.
• Exogenous testosterone (Tp) exhibited similar antioxidant and anti-inflammatory properties, protecting against MTX toxicity.

Conclusions:

• Enhancing endogenous androgenic activity with LET and GSE protects spermatogenesis against MTX-induced testicular toxicity.
• Testosterone's protective effects are attributed to its antioxidant and anti-inflammatory actions.
• LET, GSE, and testosterone show promise in mitigating MTX-induced testicular damage.