The genetic tale of transgenerational epigenetic inheritance has just received a tasty twist in its latest installment focused on intergenerational effects. The latest story of this cereal … serial reveals how folate deficiency in the paternal diet influences embryonic development through H3K4me3 transmission.
In a previous study, the lab of Sarah Kimmins (McGill University, Montreal, Canada) examined a mouse model overexpressing KDM1A, which is a H3K4 demethylase, and showed that paternal H3K4me3 aberrations escape sperm and embryonic reprogramming, thereby altering gene expression profiles in the next generation. Now, after adding diet to the mix, first author Ariane Lismer and Co. uncover how folate-deficiency in the paternal pre-conception diet further exacerbates H3K4me3 aberrations in sperm and intensifies embryonic gene expression deregulation and birth defects in offspring. Their findings will certainly give you some food for thought.
- A folate-deficient diet starting at 3 weeks of age in both wild-type and KDM1A-overexpressing male mice results in increased pre- and post-implantation pregnancy loss when bred with wild-type females
- Paternal folate-deficiency causes birth defects in offspring and the phenotype is more severe in litters sired from KDM1A-overexpressing males
- Skeletal analysis of embryos at birth showed malformations including crooked sternebrae, unfused sternebrae cartilage, asymmetrical bones, and bent ribs
- Folate-deficiency in KDM1A-overexpressing males leads to more severe abnormalities in offspring, such as missing bones, spinal defects and under-ossified skulls
- Folate deficiency alters sperm H3K4me3 in promoters and putative enhancers of developmental importance, with KDM1A-overexpressing males showing exacerbated H3K4me3 changes
- Folate deficiency-induced H3K4me3 aberrations in sperm are inherited by the preimplantation embryo and cause aberrant embryonic gene expression
Paleo, vegan, ketogenic… There are so many diets out there, but as we discover tangible scientific evidence about how specific nutritional environments can directly influence our epigenome, an epigenetic diet could be next on the horizon for prospective fathers.
Get the whole enchilada in Developmental Cell, February 2021.