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Updated: Aug 30, 2026

A Seminiferous Tubule Squash Technique for the Cytological Analysis of Spermatogenesis Using the Mouse Model
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A Seminiferous Tubule Squash Technique for the Cytological Analysis of Spermatogenesis Using the Mouse Model

Published on: February 6, 2018

5-aza-2'-deoxycytidine induces alterations in murine spermatogenesis and pregnancy outcome

Tamara L J Kelly1, En Li, Jacquetta M Trasler

  • 1Departments of Pediatrics, McGill University, and McGill University-Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada.

Journal of Andrology
|October 29, 2003
PubMed

Insights

Paternal treatment with 5-aza-2'-deoxycytidine impacts mouse fertility and sperm DNA methylation. Lowering DNA methyltransferase 1 (DNMT1) levels partially mitigates these adverse effects on male germ cell development.

Area of Science:

  • Epigenetics
  • Reproductive Toxicology
  • Cancer Therapeutics

Background:

  • Cytidine analogues like 5-aza-2 eal-deoxycytidine are investigated for anticancer therapy due to their DNA hypomethylation effects.
  • The role of DNA methyltransferase 1 (DNMT1) in mediating these effects and potential impacts on male reproduction are not fully understood.

Purpose of the Study:

  • To investigate the effects of paternal 5-aza-2 eal-deoxycytidine exposure on mouse spermatogenesis and progeny outcomes.
  • To determine if reduced DNMT1 levels modulate the adverse effects of 5-aza-2 eal-deoxycytidine on male fertility.

Main Methods:

  • Adult male mice with wild-type (Dnmt1(+/+)) and deficient (Dnmt1(c/+)) DNMT1 levels were treated with varying doses of 5-aza-2 eal-deoxycytidine.
  • Evaluated testicular weight, sperm counts, histological abnormalities, and fertility parameters (pregnancy rate, preimplantation loss).
  • Assessed global DNA methylation levels in sperm DNA.

Main Results:

  • 5-aza-2 eal-deoxycytidine treatment caused dose-dependent decreases in testicular weight, increased abnormalities, and reduced sperm counts in wild-type mice.
  • Dnmt1-deficient mice showed less severe testicular effects compared to wild-type mice.
  • Paternal drug exposure reduced pregnancy rates and increased preimplantation loss; Dnmt1 deficiency partially protected against reduced pregnancy rates.

Conclusions:

  • Paternal 5-aza-2 eal-deoxycytidine administration impairs male germ cell development and fertility in mice, associated with decreased sperm DNA methylation.
  • Reduced DNMT1 levels offer partial protection to the seminiferous epithelium against the detrimental effects of 5-aza-2 eal-deoxycytidine.
  • These findings highlight potential reproductive risks associated with DNA-demethylating agents.

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