Folate Deficiency – 5 Generations – Epigentic Inheritance – Implications for Autism

Mutation in Folate Metabolism Causes Epigenetic Instability and Transgenerational Effects on Development

Graphical and Video Presentation at link – A must.

  • Highlights
  • Mutation in the Mtrr gene causes abnormal folate metabolism in mice
  • Mtrr genotype of maternal grandparent affects development of wild-type grandprogeny
  • Placentas of wild-type grandprogeny display widespread epigenetic instability
  • Mtrr mutation impacts both the in utero environment and epigenetic inheritance


The importance of maternal folate consumption for normal development is well established, yet the molecular mechanism linking folate metabolism to development remains poorly understood.

The enzyme methionine synthase reductase (Mtrr) is necessary for utilization of methyl groups from the folate cycle.

We found that a hypomorphic mutation of the mouse Mtrr gene results in intrauterine growth restriction, developmental delay, and congenital malformations, including neural tube, heart, and placental defects.

Importantly, these defects were dependent upon the Mtrr genotypes of the maternal grandparents.

Furthermore, we observed widespread epigenetic instability associated with altered gene expression in the placentas of wild-type grandprogeny of Mtrr-deficient maternal grandparents.

Embryo transfer experiments revealed that Mtrr deficiency in mice lead to two distinct, separable phenotypes: adverse effects on their wild-type daughters’ uterine environment, leading to growth defects in wild-type grandprogeny, and the appearance of congenital malformations independent of maternal environment that persist for five generations, likely through transgenerational epigenetic inheritance.


Further Readings of Interest

This entry was posted in Autism, co-morbid, Environment, Epigenetics, Mice, Neurology, Physiology, Treatment. Bookmark the permalink.

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s