title: Effect of temozolomide on male gametes: an epigenetic risk to the offspring?
abstract: BACKGROUND
  Temozolomide is an oral alkylating agent with proven efficacy in recurrent high-grade glioma. The antitumour activity of this molecule is attributed to the inhibition of replication through DNA methylation. However, this methylation may also perturb other DNA-dependent processes, such as spermatogenesis. The ability to father a child may be affected by having this treatment. Here we report a pregnancy and a baby born after 6 cures of temozolomide.
  
  
  METHODS
  The quality of gametes of the father has been studied through these cures and after the cessation of treatment. Sperm parameters, chromosomal content and epigenetic profiles of H19, MEST and MGMT have been analysed.
  
  
  RESULTS
  Sperm counts decrease significantly and hypomethylation of the H19 locus increase with time even staying in the normal range.
  
  
  CONCLUSIONS
  This is the first report of an epigenetic modification in sperm after temozolomide treatment suggesting a potential risk for the offspring. A sperm cryopreservation before the initiation of temozolomide treatment should be recommended.
authors: AP-HP; Hopital Tenon, CECOS, 4 rue de la Chine, 75020, Paris, France.
authors: I
authors: I
authors: Berthaut
authors: D
authors: D
authors: Montjean
authors: L
authors: L
authors: Dessolle
authors: K
authors: K
authors: Morcel
authors: F
authors: F
authors: Deluen
authors: C
authors: C
authors: Poirot
authors: A
authors: A
authors: Bashamboo
authors: K
authors: K
authors: McElreavey
authors: C
authors: C
authors: Ravel
mesh_terms: D000328:Adult; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D005854:Germ Cells / Q000187:drug effects*; D005910:Glioma / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D011247:Pregnancy; D011506:Proteins / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects*; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: C094335:H19 long non-coding RNA; D011506:Proteins; D062085:RNA, Long Noncoding; D025521:Tumor Suppressor Proteins; C103637:mesoderm specific transcript protein; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide
references: Am J Hum Genet. 2003 May;72(5):1338-41
references: 12772698
references: Am J Hum Genet. 2003 Jan;72(1):156-60
references: 12439823
references: N Engl J Med. 2005 Mar 10;352(10):997-1003
references: 15758010
references: Hum Mol Genet. 2007 Nov 1;16(21):2542-51
references: 17636251
references: Cancer. 2010 Jun 15;116(12):2868-77
references: 20564393
references: Clin Oncol (R Coll Radiol). 2012 May;24(4):311
references: 22449791
references: Gynecol Obstet Fertil. 2010 Nov;38(11):660-2
references: 21030284
references: J Neurooncol. 2005 Jun;73(2):185
references: 15981111
references: Nat Rev Neurol. 2010 Jan;6(1):39-51
references: 19997073
references: Science. 2010 Dec 24;330(6012):1824-7
references: 21205669
references: Hum Reprod. 2008 Feb;23(2):251-8
references: 18083744
references: Hum Reprod Update. 2010 May-Jun;16(3):231-45
references: 19934213
references: Lancet Oncol. 2009 May;10(5):459-66
references: 19269895
references: J Oncol Pharm Pract. 2013 Dec;19(4):321-7
references: 23292971
references: Mol Hum Reprod. 2007 Jul;13(7):461-4
references: 17494104
references: Lancet. 2004 May 22;363(9422):1700-2
references: 15158633
references: Mol Hum Reprod. 2008 Feb;14(2):67-74
references: 18178607
references: Eur J Hum Genet. 2010 Jan;18(1):73-80
references: 19584898