Methotrexate induces germ cell apoptosis and impairs spermatogenesis in a rat

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Igor Sukhotnik1, Omri Nativ, Alex Roitburt

  • 1The Bruce Rappaport Faculty of Medicine, Laboratory of Intestinal Adaptation and Recovery, Technion-Israel Institute of Technology, Haifa, Israel. igor-dr@internet-zahav.net

Pediatric Surgery International
|December 11, 2012
PubMed
Abstract

Insights

Methotrexate (MTX) exposure significantly increases germ cell apoptosis and impairs spermatogenesis in rat testes. This study reveals MTX

Area of Science:

  • Reproductive Toxicology
  • Cell Biology
  • Pharmacology

Background:

  • Methotrexate (MTX) is known for toxic effects including myelosuppression and intestinal mucositis.
  • Understanding MTX's impact on male reproductive health is crucial.

Purpose of the Study:

  • To investigate the effects of methotrexate (MTX) on germ cell apoptosis.
  • To evaluate the impact of MTX on spermatogenesis in a rat model.

Main Methods:

  • Male Sprague-Dawley rats were administered MTX (20 μg/kg) or vehicle.
  • Spermatogenesis was assessed using Johnsen's criteria and germinal cell layer counts.
  • Germ cell apoptosis was quantified via TUNEL assay, and Bax/Bcl-2 protein levels were analyzed by Western blotting.

Main Results:

  • MTX treatment significantly increased germ cell apoptosis threefold on day 2 post-administration (p=0.002).
  • By day 4, MTX-treated rats showed impaired spermatogenesis, including fewer germinal cell layers and lower Johnsen's scores.
  • Increased apoptosis correlated with elevated Bax/Bcl-2 protein ratios.

Conclusions:

  • Methotrexate induces germ cell apoptosis in rat testes.
  • MTX exposure leads to impaired spermatogenesis.

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