Epigenetics and Infertilty

priyalkumar08
1 hour ago
4 min read

What is infertility?

Infertility is defined as the inability to get pregnant after one year of trying. It is a complex condition affecting 8-12% of couples of reproductive age. It can be caused by a combination of genetic, environmental and lifestyle factors. It can be divided into primary and secondary infertility. Primary infertility refers to when pregnancy never occurred and secondary infertility refers to failure to conceive subsequently after a pregnancy has occurred.

Male and Female infertility

Infertility can be attributed to one or both partners. Approximately, 20-30% of the cases are due to male infertility, 20-35% due to female infertility, 20-40% due to both male and female infertility, and 10-20% of the cases have unknown causes.

Female infertility can be caused due to

Ovulatory disorders such as polycystic ovarian syndrome, primary ovarian insufficiency and hypothalamic dysfunction. All these conditions prevent the release of a viable egg from the ovaries.
Tubal obstructions prevent the egg from passing the fallopian tubes to meet the sperm. Additionally, fibroids, polyps and congenital malformations in the uterus can impact successful implantation of the fertilized egg.
Other factors such as age, lifestyle choices, stress and certain medical conditions such as diabetes, thyroid disorders, autoimmune diseases and obesity can negatively impact female infertility.

Male infertility can be caused due to

Abnormal sperm function, production or release leading to low sperm count , poor sperm motility, abnormal sperm morphology and even complete absence of sperm.
Testicular damage or disease, genetics, and hormonal imbalances.
Environmental factors such as exposure to toxins, obesity, and substance abuse.

What is Epigenetics?

Epigenetics refers to how environmental exposures can lead to heritable changes or modifications to the DNA without altering the sequence of the DNA. These modifications regulate gene expression. Epigenetic regulation of gene expression has significant implications for fertility and reproductive health.

Epigenetic mechanisms

DNA Methylation is the most common epigenetic mechanism. It involving addition of a methyl group to regions of the DNA rich in CpG dinucelotides known as CpG islands (CGIs). These CGIs are found in promoter regions of genes. Methylation of these regions regulate gene expression, turning on genes when unmehtylated or turning off genes when methylated. Abnormal DNA methylation patterns have been shown to be associated with infertility.
Histone modifications particularly acetylation (addition of acetyl group) and methylation (addition of methyl) play an important role in regulating expression of genes required for normal reproductive function. The DNA is wrapped around proteins called histones and organized into chromatin. The degree to which the DNA wraps around these histones determines whether the genes will be active or not. Highly compact wrapping (condensed chromatin) results in genes being inactive and loose wrapping (uncondensed) results in genes being active. Acetylation of histones occurs on loosely packed chromatin resulting in gene activation. Methylation on the other hand can occur on condensed or uncondensed chromatin and result in activation or inactivation of genes depending on the site and degree of methylation (mono-, di or tri-methylation).
Non coding RNAs (ncRNAs) are functional RNA molecules that do not encode for a protein and regulate gene expression.

Environment, Epigenetics, and Infertility

Environmental factors have significant implications for infertility in men and women.

Endocrine-disrupting chemicals (EDC), are a group of chemical compounds found in everyday products such as cosmetics, food and beverage packaging, toys, and pesticides. Exposure to EDC can occur through air, water, skin, and diet and can lead to disruption of the endocrine system. Although EDC cannot be completely avoided, making informed choices can help reduce exposure and associated health risks.
Exposure to heavy metals such as arsenic, lead, mercury, and cadmium negatively impacts fertility by disrupting the endocrine system and altering the epigenetic regulation of genes involved in fertility.
Lifestyle, diet and nutrition are other factors that affect fertility. Prevalence of unhealthy habits like cigarette smoking, alcohol consumption, stress, and inadequate physical activity are associated with lower fertility rates. These factors are highly individualistic and depend on the persons genetic and epigenetic predisposition.

Current diagnostic and therapeutic tools

The current diagnostic tools to detect epigenetic changes include detecting DNA methylation patterns, histone modifications and non coding RNA expression. These tools are a combination of molecular and computational methods. Bisulfite sequencing is the most commonly used method for detecting DNA methylation patterns, chromatin immunoprecipitation (ChIP) is used to detect histone DNA interactions as well as histone modifications and RNA sequencing methods are used to detect levels of non coding RNAs. These tools have limitations in terms of cost effectiveness and require the use of specialized equipment and expertise making them inaccessible to many laboratories. Therefore, there is a need for streamlined, cost effective, accessible diagnostics tools that can be used in a clinical setting.

Current therapeutic strategies include the use of DNA methylation inhibitors, histone deacetylase inhibitors and non coding RNA therapies. Although current therapies show promise, they do pose a significant challenge in fertility treatments due to lack of tissue specificity which can lead to severe side effects. This warrants is a need for the development of safe and effective tissue specific treatment for successful outcomes.

Sources

Assessed and Endorsed by the MedReport Medical Review Board