Genetic Causes of Male Infertility — Genetic Lifehacks

Struggling to get pregnant as a couple? You’re not alone. The World Health Organization now estimates that almost 10% of couples worldwide are dealing with fertility issues. And the problem of infertility seems to be equally split between males and females.[ ref]

Many different genetic variants can increase the risk of infertility in men. These variants impact different aspects of sperm production — from hormones to oxidative stress to DNA damage repair. My goal here is to help you understand where you are more likely to have genetic susceptibility to infertility. This can help you target the right lifestyle interventions and supplements.

Male Infertility: Getting to the root cause

Infertility is formally defined as an inability to become pregnant after 12-months of unprotected sex. There are a number of factors influencing infertility: genetic mutations, environmental exposure, physical abnormalities, and the combination of environmental factors with genetic susceptibility from common variants.

For most couples facing infertility, the first thing to do is go to a fertility specialist. The doctor can help rule out physical abnormalities or major hormone alterations.

But what happens when infertility is labeled ‘idiopathic’, which is medical-speak for ‘unknown origin’? That is when you need to dig deeper into lifestyle and genetic susceptibility.

How is sperm produced?

Men produce sperm constantly through a process called spermatogenesis. On average, hundreds of millions of precursor sperm cells are generated daily in the seminiferous tubules. From there, they go through a series of events, resulting in mature spermatozoa that are stored in the epididymis.

The whole process takes around three months. This time scale of three months is important when you are experimenting with lifestyle changes to make a difference for infertility. Patience, along with targeted interventions, are key.[ ref]

Defining normal sperm concentrations:

When you start reading the research on male infertility causes, you’ll come across several technical terms for defining alterations in sperm concentration and motility.

• oligozoospermia = decreased sperm concentration (defined as < 15 ×106sperm/ml)
• asthenozoospermia = decreased sperm motility (progressive motility ❤2% or total sperm mobility under 40%)
• teratospermia = majorly decreased sperm motility (sperm motility of <4%)
• oligoasthenoteratozoospermia = combination of all of the above

Essentially, this boils down to not having enough healthy sperm or not having enough sperm motility. Or both.

Oxidative Stress: Lifestyle, diet, inflammation

Research shows that one of the most significant sources of male infertility is oxidative stress, accounting for about half (somewhere between 30–80%)

Oxidative stress is defined as cells producing more reactive oxygen species ( ROS) than they can balance out with antioxidants.[ ref]

Sperm are particularly vulnerable to oxidative stress due to the cell membranes being rich in unsaturated fatty acids, which are more prone to oxidation when ROS is out of balance.[ ref]

Excess ROS can also damage DNA in sperm, which is more of a problem than in normal cells due to a lack of enzymes to combat oxidative stress.[ ref]

One research study states:

“The oxidative stress, which refers to an imbalance in levels of reactive oxygen species (ROS) and antioxidants, is one of the main causes of infertility in men.”[ ref]

For motility, sperm need a lot of energy and thus have a lot of mitochondria in the flagellum. Excess oxidative stress impairs the mitochondria, leading to decreased motility.[ ref]

Sources of oxidative stress:

Poor diet: A diet of fast food, junk food, and beer is a recipe for male infertility. Not only is your body fighting against the additives and oxidized fats in junk food, but the antioxidants from vegetables or organ meats are needed for fighting oxidative stress.

Cigarette smoking: Smoking is associated with reduced sperm count and decreased sperm quality.[ ref] Cannabis use is also linked to reduced sperm count and an increase in abnormal sperm.[ ref]

Excessive alcohol consumption: Alcohol consumption is also linked to decreased sperm function in men with infertility.[ ref]

Stress/ HPA axis alterations: High levels of ROS not only leads to oxidative stress but also causes a disruption in male sex hormones via the HPA axis. Additionally, stress causes HPA axis alterations and increases inflammatory cytokines. Thus, stress can cause infertility in two ways: social/psychological stress or physical stress caused by ROS.[ ref][ ref]

Heat stress: Excessive heat in the testes increases oxidative stress and disrupts mitochondrial energy production. It can also decrease testosterone and luteinizing hormone levels. Heat stress also impacts the HPA axis and hormone levels.[ ref]

Environmental toxicants: Exposure to mercury, cadmium, BPA, and dioxin are all linked to infertility. Endocrine-disrupting chemicals may also be a problem for some men.[ ref]

Hormone alterations:

Men with infertility, on average, have higher estradiol levels. Estradiol is a type of estrogen. Essentially, higher estrogen levels lead to a decrease in spermatogenesis.[ ref] Higher estrogen could be due to obesity, conversion of testosterone to estrogen, or estrogen-mimicking chemicals.

Rare mutations in the androgen receptor gene can also cause infertility.[ ref]

Other Lifestyle / Environmental Causes:

Obesity “For instance, obesity is associated with male infertility, likely because of hormonal changes secondary to excess adipose tissue. In a retrospective multi-institutional cohort study, Bieniek et al. demonstrated an inverse relationship between body mass index (BMI) and testosterone, testosterone-to-estradiol ratio, ejaculate volume, sperm concentration, and morphology . The authors also reported higher rates of azoospermia and oligospermia among obese men (12.7% and 31.7%, respectively) compared with men of normal weight (9.8% and 24.5%) .”[ ref]

Medications: Certain drugs, such as anabolic steroids, SSRIs, methotrexate, cannabis, and sulfasalazine, are linked to a higher risk of infertility.[ ref][ ref][ ref] If you are on prescription medication, talk with your doctor about infertility as a side effect.

Varicoceles, the abnormally dilated and twisted veins in the pampiniform plexus, are a common cause of male infertility. Varicoceles are present in ~15 to 20% of men and 35 to 40% of infertile men, thus doubling the risk of infertility.[ ref]

Hyperglycemia: High blood glucose levels reduce sperm. It is partly because of increased oxidative stress, but other changes to sperm function also are seen in men with diabetes.[ ref]

Genetic Variants Linked to Male Infertility:

View the rest of this article, including specific genes to check, on GeneticLifehacks.

Originally published at https://www.geneticlifehacks.com on November 1, 2021.