Trans Species RNA Activity: Sperm RNA of the Father of an Autistic Child Programs Glial Cells and Behavioral Disorders in Mice.
Zeynep YilmazKeziban Korkmaz BayramEcmel MehmetbeyogluZuleyha DoganyigitFeyzullah BeyazElif Funda SenerSerpil TaheriYusuf OzkulMinoo RassoulzadeganPublished in: Biomolecules (2024)
Recently, we described the alteration of six miRNAs in the serum of autistic children, their fathers, mothers, siblings, and in the sperm of autistic mouse models. Studies in model organisms suggest that noncoding RNAs participate in transcriptional modulation pathways. Using mice, approaches to alter the amount of RNA in fertilized eggs enable in vivo intervention at an early stage of development. Noncoding RNAs are very numerous in spermatozoa. Our study addresses a fundamental question: can the transfer of RNA content from sperm to eggs result in changes in phenotypic traits, such as autism? To explore this, we used sperm RNA from a normal father but with autistic children to create mouse models for autism. Here, we induced, in a single step by microinjecting sperm RNA into fertilized mouse eggs, a transcriptional alteration with the transformation in adults of glial cells into cells affected by astrogliosis and microgliosis developing deficiency disorders of the 'autism-like' type in mice born following these manipulations. Human sperm RNA alters gene expression in mice, and validates the possibility of non-Mendelian inheritance in autism.
Keyphrases
- gene expression
- induced apoptosis
- intellectual disability
- autism spectrum disorder
- early stage
- cell cycle arrest
- high fat diet induced
- mouse model
- nucleic acid
- young adults
- transcription factor
- oxidative stress
- cell proliferation
- endoplasmic reticulum stress
- endothelial cells
- squamous cell carcinoma
- cell death
- genome wide
- spinal cord
- gestational age
- lymph node
- low birth weight
- induced pluripotent stem cells
- pi k akt