Apr 6, 2020

Paternal exposure to the pesticide DDT induces intergenerational programming of breast cancer predisposition via sperm miRNA

BioRxiv : the Preprint Server for Biology
Matthew ZeffermanSonia de Assis


Background: DNA sequence accounts for the majority of disease heritability, including cancer. However, it is becoming clear that environmentally-induced epigenetic inheritance can also occur. Epidemiological studies have shown that maternal exposure to the pesticide DDT in pregnancy is associated with increased breast cancer risk in women. Yet, the effects of paternal exposure to this and other pesticides on the progeny breast cancer development has not been investigated. Methods: Male mice (c57bl/6) were exposed to DDT or to a control-vehicle (CO) solution and used for sperm collection or mating with unexposed females to produce the DDT or CO daughters. In another experiment, normal mouse embryos (zygote stage) were injected with miRNA-10b and implanted into surrogate mothers to produce miR-10b offspring. DDT daughters or miRNA-10b females were used to study breast cancer development and metabolic parameters. Paternal sperm was used for RNA-seq analysis and miRNA expression levels. Results: Pre-conception paternal DDT exposure altered the sperm small non-coding RNA load, with an increase in miRNAs and a specific surge in miRNA-10b levels. DDT offspring weighed less at birth and at weaning, but became overweight and showed meta...Continue Reading

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Mentioned in this Paper

Coculture Techniques
Thyroid Hormone Plasma Membrane Transport Defect
Objective (Goal)
Pharmacologic Substance
Laboratory Culture
Idiosyncratic Drug Effect

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