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Pre-conceptional maternal exposure to cyclophosphamide results in modifications of DNA methylation in F1 and F2 mouse oocytes: evidence for transgenerational effects.
- Source :
-
Epigenetics [Epigenetics] 2019 Nov; Vol. 14 (11), pp. 1057-1064. Date of Electronic Publication: 2019 Jun 19. - Publication Year :
- 2019
-
Abstract
- Cyclophosphamide (CPM), an agent widely used in breast cancer therapy, has strong gonadotoxic effects. Female reproductive potential after therapy relies on ovulated oocytes deriving from primordial follicles surviving CPM toxic insult. In this study, we investigated in the mouse model whether pre-conceptional maternal exposure to CPM has epigenetic effects on offspring oocytes and if they are inherited. Adult female mice mated following CPM exposure, generated an offspring (F1) with delayed growth, normal fertility and altered methylation of three imprinted genes ( H19, Igf2r and Peg3 ) in their oocytes. These alterations were present in oocytes generated by F2 mice. Pre-conceptional maternal exposure to fertoprotective agents AS101 and crocetin prior to CPM was not able to fully counteract alterations in offspring oocyte imprinting. For the first time, current study evidences that pre-conceptional CPM maternal exposure can affect the competence of offspring's oocytes and warns on possible long-term effects on the health of next generations.
- Subjects :
- Animals
Female
Kruppel-Like Transcription Factors genetics
Kruppel-Like Transcription Factors metabolism
Male
Mice
Oocytes metabolism
RNA, Long Noncoding genetics
RNA, Long Noncoding metabolism
Receptor, IGF Type 2 genetics
Receptor, IGF Type 2 metabolism
Cyclophosphamide pharmacology
DNA Methylation
Genomic Imprinting
Maternal Exposure
Mutagens pharmacology
Oocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1559-2308
- Volume :
- 14
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Epigenetics
- Publication Type :
- Academic Journal
- Accession number :
- 31189412
- Full Text :
- https://doi.org/10.1080/15592294.2019.1631111