1. Pre-conceptional maternal exposure to cyclophosphamide results in modifications of DNA methylation in F1 and F2 mouse oocytes: evidence for transgenerational effects
- Author
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Sara Franchi, Martina Placidi, Giulia Rossi, Giovanna Di Emidio, Paolo Giovanni Artini, Carla Tatone, Marco D'Aurora, Liborio Stuppia, and Valentina Gatta
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Cyclophosphamide ,Offspring ,Kruppel-Like Transcription Factors ,AS101 ,crocetin ,epigenetics ,fertility ,imprinting ,oocyte ,Biology ,Receptor, IGF Type 2 ,Andrology ,Genomic Imprinting ,Mice ,03 medical and health sciences ,0302 clinical medicine ,parasitic diseases ,medicine ,Animals ,Epigenetics ,Imprinting (psychology) ,Molecular Biology ,Brief Report ,Insulin-like growth factor 2 receptor ,DNA Methylation ,Oocyte ,030104 developmental biology ,medicine.anatomical_structure ,Maternal Exposure ,030220 oncology & carcinogenesis ,embryonic structures ,DNA methylation ,Oocytes ,Female ,RNA, Long Noncoding ,Genomic imprinting ,human activities ,Mutagens ,medicine.drug - 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.
- Published
- 2019