Tag Archives: embryonic stem cells

How dad’s bad diet may have impacted your disease risk

We all know that expecting moms need to take good care of themselves, so that the environment in the womb is as optimal as possible to reduce disease risk to the developing fetus. That means eating a healthy well balanced diet, achieving the appropriate amount of weight gain during pregnancy, managing metabolic problems like gestational diabetes if they arise, and avoiding harmful exposures like alcohol and recreational drugs.

Evidence shows that a father's diet prior to conception, may impact gene expression and future health, in his offspring.

Evidence shows that a father’s diet prior to conception, may impact gene expression and future health, in his offspring.

A growing body of evidence now also implicates a role for dad in the risk of disease imparted to the fetus. By this, we’re not speaking of the inheritance of genetic mutations, but instead effects that arise in the father due to his environmental exposures, which are then passed onto the fetus at the time of conception. These types of inheritable traits are known as epigenetic, as opposed to genetic, because they are not passed on from parent to child through changes in the DNA. In rats, it has been shown that there is good evidence that dad’s diet can have an influence on his offspring’s risk for diabetes, high blood pressure, and high cholesterol (Rando and Simmons). But, if these risks are not passed from father to offspring by the inheritance of his DNA, then how is the affect passed on? In the January 22, 2016 issue of the journal Science, Oliver Rando, in Lyon, France demonstrates one possible mechanism, by which the environment of the father, prior to fertilization of the mother’s egg with his sperm, leads to profound and long-lasting changes in the development of their fetus.

Dr. Rando, and his team, were able to show that when male rats were fed a diet low in protein, there was a measurable shift in the number and types of small RNA molecules found in their mature sperm. A significant increase was observed in the amount of certain transfer-RNA (tRNA) molecules in the sperm of male rats fed the low protein diet versus those on a normal diet. The conventional function of tRNA is to deliver amino acids to the ribosome, so they can be joined together to make a protein. There are different tRNAs molecules that are specific for each amino acid.

Upon fertilization of the egg cell, the sperm introduces small RNA molecules which influence genetic programming of the developing embryo.

Upon fertilization of the egg cell, the sperm introduces small RNA molecules which influence genetic programming of the developing embryo.

Rando’s team found that the increase in sperm tRNA, seen in low protein fed rats, were not whole molecules, but only fragments of tRNA. The tRNA fragments were not produced by the developing sperm cells themselves, as might be expected, but were fragmented in other cells of the male reproductive tract, then transferred into the sperm as they underwent their maturation process. Upon fertilization of the egg, these small RNAs enter the egg from the sperm, altering expression of genes in the developing embryo. Using embryonic stem cells, it was shown that the effect of these tRNA fragments in the fertilized egg, is at least in part, realized by the changes they produce an endogenous retroelement called MERVL, a factor known to be an important in enhancing gene expression in the early embryo. This ultimately leads to an over expression of some genes along the cholesterol pathway in the developing fetal liver, potentially influencing future metabolic health.

The dietary changes in the male rats led to changes in the the small RNA molecules in their reproductive tract, which were transferred into their sperm, ultimately affecting gene expression in the fertilized egg, and adversely affecting the risk of disease in the offspring. It is not known if these same mechanisms would apply to humans -although there is no reason to think that they might not – or which other environmental exposures of the future father could also be important in the health of his offspring. It may still be too early to make any evidence based recommendations for guys hoping to start a family, but perhaps further research will help better define how much impact diet, exercise, and other habits have on their future health of their sons and daughters.

 

Reference Articles:
1. Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals.
Science. 2016 Jan 22;351(6271):391-6. doi: 10.1126/science.aad6780. Epub 2015 Dec 31.
Sharma U1, Conine CC1, Shea JM1, Boskovic A1, Derr AG2, Bing XY1, Belleannee C3, Kucukural A2, Serra RW1, Sun F1, Song L1, Carone BR1, Ricci EP4, Li XZ5, Fauquier L1, Moore MJ6, Sullivan R3, Mello CC7, Garber M2, Rando OJ

2. I’m eating for two: parental dietary effects on offspring metabolism.Cell. 2015 Mar 26;161(1):93-105. doi: 10.1016/j.cell. 2015.02.021.
Rando OJ1, Simmons RA2.

3. Retrotransposons shape species-specific embryonic stem cell gene expression. Luisa Robbez-Masson and Helen M Rowe
Retrovirology201512:45 DOI: 10.1186/s12977-015-0173-5

4. Regulation of Mouse Retroelement MuERV-L/MERVL Expression by REX1 and Epigenetic Control of Stem Cell Potency
Front Oncol. 2014; 4: 14. Published online 2014 Feb 6. doi:  10.3389/fonc.2014.00014
Jon Schoorlemmer,1,2,* Raquel Pérez-Palacios,1 María Climent,3,† Diana Guallar,1,† and Pedro Muniesa3

Scientists have used sugar-coated scaffolding to move a step closer to the routine use of stem cells in the clinic and unlock their huge potential to cure diseases from Alzheimer’s to diabetes. (c) University of Manchester

Sugar-coated scaffolding guides and differentiates stem cells

One of the miracles of modern day medicine science, stem cells, are regarded by scientists as the basic building blocks for devising treatments, cures or transplants for some of today’s yet incurable diseases like Alzheimer or diabetes. The biggest hurdle researchers face is differentiating stem cells so that they may grow into a specific type of cell. Researchers at Manchester University may have come across a breakthrough in leaping this particular issue after they used sugar-coated scaffolds to guide embryonic stem cells so that they may develop into specific types of somatic cells.

Scientists have used sugar-coated scaffolding to move a step closer to the routine use of stem cells in the clinic and unlock their huge potential to cure diseases from Alzheimer’s to diabetes. (c) University of Manchester

Scientists have used sugar-coated scaffolding to move a step closer to the routine use of stem cells in the clinic and unlock their huge potential to cure diseases from Alzheimer’s to diabetes. (c) University of Manchester

The web-like biomaterial is made out of sugar molecules using a technique called electrospinning, which employs an electrical charge to draw very tiny fibres from a liquid, mimicking structures that occur in nature. These long, linear sugar molecules or meshes have shown in previous research that play a fundamental role in stem cell transformation and regulation of behavior. This combination of sugar molecules with the fibre web, provides both biochemical and structural signals which guide ESCs into becoming specific types of somatic cells.

Lead author Dr Catherine Merry, from Manchester’s Stem Cell Glycobiology group, said: “These meshes have been modified with long, linear sugar molecules, which we have previously shown play a fundamental role in regulating the behaviour of stem cells. By combining the sugar molecules with the fibre web, we hoped to use both biochemical and structural signals to guide the behaviour of stem cells, in a similar way to that used naturally by the body. This is the Holy Grail of research into developing new therapeutics using stem cell technology.”

Whether the Holy Grail claim is a worthy assumption, that remains to be seen. What’s certain is that if the researchers’ technique can be scaled, a range of applications might be opened up for it from tissue engineering, where the meshes could support cells differentiating to form bone, liver or blood vessels, and much more. The meshes also have potential therapeutic implications in the treatment of diseases such as multiple osteochondroma (MO), a rare disease creating bony spurs or lumps caused by abnormal production of these sugar molecules.

Co-author Professor Tony Day, from Manchester’s Wellcome Trust Centre for Cell-Matrix Research, said: “This cross-faculty collaboration provides exciting new possibilities for how we might harness the adhesive interactions of extracellular matrix to manipulate stem cell behaviour and realise their full therapeutic potential.”

Findings were published in the Journal of Biological Chemistry.