Effects of amifostine in combination with cyclophosphamide on female reproductive system

Reprod Sci. 2012 May;19(5):539-46. doi: 10.1177/1933719111426599. Epub 2012 Jan 19.

Abstract

This study investigated the cytoprotective effects of amifostine against the adverse effects of cyclophosphamide relying on ovarian cell death markers and the fertilization rate of the surviving follicles as a late outcome of the study. Combined pretreatment of amifostine with cyclophosphamide enabled partial recovery of antiapoptotic messenger RNA (mRNA) expression levels while a decrease in expression of BAX and Casp3 were identified. The pretreatment of amifostine to cyclophosphamide significantly reduced the proportion of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive primary and preantral follicles (P < .001 and P < .05, respectively). These findings were comparable with the results obtained from protein expression of cleaved caspase 3. The fertilization rate showed a significant capability of amifostine to improve fertilization potency of oocytes exposed to cyclophosphamide (P < .01). In conclusion, administration of amifostine prior to cyclophosphamide might serve as a promising protocol to improve female fertility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amifostine / administration & dosage*
  • Animals
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Apoptosis / drug effects
  • Caspase 3 / genetics
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects*
  • Cytoprotection / drug effects
  • Embryo Culture Techniques
  • Female
  • Fertility Preservation / methods*
  • Fertilization in Vitro
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Inbred BALB C
  • Oocytes / cytology
  • Oocytes / drug effects*
  • Oocytes / physiology
  • Ovarian Follicle / drug effects
  • Ovary / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • bcl-2-Associated X Protein / genetics

Substances

  • Antineoplastic Agents, Alkylating
  • bcl-2-Associated X Protein
  • Cyclophosphamide
  • Caspase 3
  • Amifostine