A short introduction to epigenetics

What is Epigenetics?

Epigenetics is a normal gene regulatory phenomenon involved in human development and cellular differentiation. Indeed, each cell type in the body is genetically identical but needs to differentiate phenotypically to sustain a normally functioning human body: neurons, skin, etc. However, there is evidence that several external factors can impact gene function epigenetically, both positively and negatively, including aging, environmental exposure, diseases like cancer, diet, and even exercise.

The field of epigenetics is relatively new and needs more research to understand if epigenetic changes actually cause disease or if they are simply correlational. Likely a bit of both. However, several companies, including publicly traded companies, are looking at creating both epigenetically-based diagnostics and therapeutics. For example, Episona is developing diagnostics that will better elucidate problems in male infertility, mental health, and cancer.

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3 Examples of Transgenerational Epigenetic Inheritance

Transgenerational Epigenetic Inheritance

Transgenerational epigenetic inheritance is the idea that epigenetic marks (i.e., DNA methylation, histone modifications) can be acquired on the DNA of one generation and stably passed on through the gametes (i.e., sperm and eggs) to the next generation. In other words, experiences and environmental exposures can change the way your DNA works (without changing the DNA itself) and this could be passed on to your offspring.

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Sperm quality and male age – paternal age effect

Sperm Quality and Male Age

Pablo Picasso had a son, Claude, when he was in his sixties. Steve Martin just had a baby girl at 67. And I believe that Nanu Ram Jogi with his youngest child, two-week-old Girija Rajkumari, sets a record for being the oldest father at 90 years old. And looking over at ancestry.com, it appears that my father’s father, John Horsager, was 55 when my dad was born (57 year’s old when my dad’s younger brother, Harley, was born). It’s well understood that women have a set number of years to reproduce as menopause defines the upper limit.

As described above, men can reproduce well into old age, assuming they remain healthy and, well, functional. Although my father, uncle, and I came out just fine (no autism or schizophrenia), growing evidence suggests that paternal age can increase the risks of these disorders in the offspring. Maybe we’ve just been lucky. What is this paternal age effect?
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Is it time for a better test for male infertility?

The Reality of Male Factor Infertility

Although it is often assumed that infertility is a woman’s problem, the reality is male factor infertility (MFI) is responsible in about 50% of the cases. Some of the time, the cause of the male factor infertility is straight forward such as structural abnormalities, sperm production disorders, ejaculatory disturbances and immunologic disorders. However, testing male factor infertility is often unsuccesful. About 30% of the time the couple’s infertility cannot be determined (called Unexplained Infertility).

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Sperm DNA methylation and brain disorders

Sperm Changes With Age   

For years it has been assumed that sperm cells are only responsible for providing the father’s DNA; the rest of the baby’s early development is the responsibility of the mother. However, several studies have shown changes in sperm epigenetics (particularly, DNA methylation) correlate to both fertilization potential as well as early development (i.e., embryogenesis). If DNA methylation plays an important role in early development, is it possible that sperm epigenetics contribute to other, later stages of development, such as brain development?

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Epigenetic biomarkers predict male infertility

Sperm Epigenetics and Male Infertility

Investigators from the University of Utah and the University of Southern California evaluated whether measuring epigenetic changes in sperm DNA could be used to predict male infertility. Philip Uren, Ph.D., a lead author on the study, said “we were surprised at how well the model discriminates fertile sperm samples from men with infertility needing IVF”.
 
Around 15% of people have some form of infertility. In about half of those cases male factors play a major role, but they’re often overlooked.

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Weight loss alters sperm epigenetics

Why study epigenetics? 

Certainly our body weight can have a significant impact on our own health, particularly if we are obese. However, how much does it shape the health of our offspring? There was a recent study by Donkin et al. that shows weight loss alters sperm epigenetics, a biological profile that is thought to be passed on across generations. You can think of epigenetics as an extra layer of information that is added to DNA by the environment. This information can change, but is also heritable.

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3 ways smoking can cause infertility in men

Many couples trying to get pregnant want to know–“Does smoking cause infertility?”.

Yes, and no.  Lifestyle factors like smoking, may or may not cause fertility problems for an individual couple. 

Human traits like behavior, health, and personality are determined by our unique genetic and epigenetic code–where both are shaped by our environment (“nature” and  “nurture”).  

The technology of current fertility tests is severely limited– up to 30% of couples are diagnosed with “unexplained infertility”. Therefore, behavioral choices like moderate and daily smoking might be affecting the fertility of the sperm in ways that we can’t see in the standard semen analysis. Here, we explore how smoking might be causing infertility in men by summarizing current scientific research and introducing an  innovative new fertility test that can provide some answers. 

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