University of California, Santa Cruz
Sperm RNA-mediated intergenerational epigenetic inheritance
The possibility that our environment and life experiences can influence the health and longevity of our future generations has tremendous implications for basic biology and public health and policy. Indeed, there is mounting evidence from worms to humans, that parental environment can influence phenotypes in future generations. However, the mechanism of such transgenerational inheritance—sometimes referred to as inheritance of acquired traits, or Lamarckian Inheritance—remains elusive. The inheritance of acquired traits was previously discredited, as there was no known mechanism for the environment to alter the genetic material (DNA) transmitted from parents to offspring. With advances in the field of epigenetics —inheritance of phenotypic changes in the absence of changes in the underlying DNA sequence— there is a resurgent interest in transgenerational inheritance. As environmental conditions can modulate epigenetic information molecules, intergenerational inheritance is potentially mediated via alterations to the epigenetic information molecules in gametes —sperm in males and eggs in females. Our laboratory aims to elucidate how our environmental conditions modulate specific epigenetic information signals in gametes and how those signals influence offspring gene expression and development.
Paternal diet can influence metabolic health in offspring. My previous studies revealed that paternal dietary information is transmitted to offspring via sperm and that small RNAs are the environmentally-responsive epigenetic molecules in sperm. Surprisingly, we found that small RNAs in mature sperm are generated in the somatic cells of the epididymis—an organ where sperm undergo post-testicular maturation and become motile— and shipped to sperm via small extracellular vesicles. Based on these studies, we hypothesize that the epididymis potentially senses paternal environmental conditions and transmits this information to sperm via vesicles. My lab is elucidating the mechanism of RNA-mediated communication between epididymis and sperm, and its consequences to offspring health. We aim to understand the mechanism of biogenesis of small RNAs in mammalian sperm and examine how exposure of an organism to various environmental conditions alters/reprograms sperm small RNA payload, and thus, offspring health. We use a unique and powerful combination of molecular, genetic, reproductive, and genomic approaches to address these questions.