A fundamental law of genetics states that progenies do not inherit epigenetically-based adaptive, pathological or neural features acquired in response to environmental conditions. However, recent studies seem to contradict this dogma. Paternal inheritance of diet-induced obesity and diabetes was first suggested by epidemiological analysis of human cohorts and later confirmed by experimental analysis. For instance, the offspring of fathers who had been undernourished during the 1944–1945 famine in The Netherlands developed increased adiposity more frequently than controls and this up until the second generation. Also, in the Overkalix cohort study, a northern Swedish community that endured year-to-year food supply variations had increased diabetes frequencies, which were linked to the grandfathers’ food availability.
In the past, histone modification and DNA methylation patterns were reported to be altered in the testis and sperm of males with metabolic disorders and a chromatin-depend signature of paternal-diet-induced intergenerational metabolic reprogramming has been identified. However, the possible roles of these epigenetic marks in transgenerational signalling are still undetermined. Now, two new studies in mice from University of Massachusetts and Beijing University, respectively, demonstrate how a father’s diet affects levels of specific small RNAs in his sperm, which in turn can affect gene regulation in offspring. The researchers state that these results add to the growing list of ways in which a male’s lifestyle can influence his offspring, including through the sperm epigenome, microbiome transfer and seminal fluid signalling.
Previous studies show that female rats born to fathers on a high-fat diet had impaired insulin secretion and glucose tolerance. Another study showed that after maternal exposure to a high fat diet, mice had increased body size and reduced insulin sensitivity and these traits were transmitted up to the third generation. Furthermore, findings have shown that the fat mass of mice raised on a high fat ‘Western-like’ diet steadily increased over four generations. In addition, male and female born to fathers fed a low protein and high sugar diet had a modified liver transcriptome; and C57BL/6 males fed a lipid-rich diet exhibited obesity in the absence of overt diabetes and transmitted the altered metabolic health to their progeny. Increasing evidence indicates that offspring metabolic disorders can result from the father’s diet, however, the mechanism remains unclear. The current studies demonstrate how RNA in sperm can be affected by diet, and that this can cause changes in gene regulation of offspring and associated metabolic disorder.
In the first study, a team of researchers led by Beijing University fertilized mouse eggs using sperm from a group of male mice fed a high-fat diet (HFD), as well as a group of male mice on a normal diet (ND). Results show that the two groups of offspring exhibited no obvious differences in body weight within 16 weeks, however, as early as seven-weeks-old, offspring whose fathers were in the HFD group developed impaired glucose tolerance and insulin resistance, which became more severe at 15 weeks.
To assess whether the fathers’ sperm RNA contributed to these differences between the HFD and ND offspring, the lab purified RNAs from the two groups of sperm and injected them into normal zygotes. Data findings show that while the HFD offspring had significantly higher blood glucose and insulin levels, their insulin sensitivity was comparable to that of ND offspring.
The group state that their findings suggest that RNAs from sperm of HFD males contain the information to induce glucose intolerance, but not insulin resistance. Further investigation identified tRNAs fragments, containing about 30-34 nucleotides, as the class of small RNA that caused the glucose intolerance observed in HFD offspring. Results show that a genome-wide comparison between ND and HFD offspring found significantly less expression of genes involved with ketone, carbohydrate, and monosaccharide metabolism in the HFD group.
In the second study, a team of researchers from the University of Massachusetts tested whether the sperm of mice on a low protein (LP) diet experienced any changes in RNA levels. Results show that small RNAs from immature sperm in the testis did not correlate with dietary effects; yet, sequencing of small RNA in mature sperm in the epididymus revealed great expression of certain RNAs. The lab then isolated RNA in sperm from LP mice and controls, finding particularly high levels of a RNA, tRNA-Gly-GCC, in the LP group. Data findings show that tRNA-Gly-GCC suppresses a subset of genes, including a gene that contributes to the plasticity of mouse embryonic stem cells.
The researchers surmise that although tRNAs are best known for roles in protein synthesis, their fragments are turning up in other cellular situations. They go on to add that both studies suggest that the RNA bits alter gene activity with the UMass team blocking one of the tRNA fragments inside embryonic stem cells to increase the activity of about 70 genes. For the future, the groups state that they to investigate how permanent these changes are and how quickly they can be reversed by changing diet. They go on to conclude that the effects of the RNA fragments don’t have to be harmful and state that if a bad diet can influence a person, a healthy diet can do it in the same way.
Source: Science Journal
Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.
Michelle has been picked up as an expert writer for Informa publisher’s Clinical Trials community, as well as being listed as a blog source by the world’s leading medical journals, including the acclaimed Nature-Springer journal series.
Healthinnovations is currently indexed by the trusted Altmetric and PlumX metrics systems, respectively, as a blog source for published research globally. Healthinnovations is also featured in the world-renowned BioPortfolio, BioPortfolio.com, the life science, pharmaceutical and healthcare portal.
Most recently the Texas A&M University covered The Top 10 Healthinnovations series on their site with distinguished Professor Stephen Maren calling the inclusion of himself and his team on the list a reflection of “the hard work and dedication of my students and trainees”.
Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.
An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.