What is Oxidative stress?

Oxidative Stress: When it first comes to mind, you might think of it as a stressed-out oxygen molecule, and you would not be that far off! 

Oxidative stress happens when there is a buildup of reactive oxygen species (ROS).¹

What is ROS?

ROS exists in different forms of oxygen, like Superoxide radicals, hydrogen peroxide, hydroxyl radicals, and singlet oxygen. ROS are produced as cells carry out important cell functions as a waste product.^2,3 

Cells depend on low levels of ROS for many important processes, such as immunity, cell communication, and the production of energy throughout the body.⁴ 

Although if the levels of ROS are too high, it can damage important parts of the cell, like proteins, fats, or genetic material.⁵ 

Many studies have shown that oxidative stress can play a role in the development and progression of several diseases, such as cancer, diabetes, metabolic disorders, and heart disease.⁶ 

ROS happens because of a disrupted balance between free radicals and antioxidants.⁷

What are free radicals and antioxidants?

Radicals like the superoxide radical (O₂^•−) and hydroxyl radical (•OH) are known as free radicals, which are atoms or groups of atoms with an unpaired number of electrons, which means their structure is ‘incomplete’, which means they are considered ‘less stable’ and so are incredibly reactive.⁵ 

They are also involved in many cellular and biological processes when kept at low or moderate levels, and so are crucial to human health.⁸ However, when there are large amounts of free radicals, they can harm cells in the body, and contribute to cancer, heart disease, stroke and other ageing/chronic diseases.⁹ Free radicals are normally regulated by antioxidants.¹⁰

Antioxidants are molecules that fight the free radicals in the body, as they use defences which neutralise the free radicals through an enzyme process¹.

The human body needs to have a balance maintained between free radicals and antioxidants to keep the body healthy and prevent diseases. When this balance is disrupted, it leads to ROS, which can lead to Oxidative Stress, which can damage or even destroy the cells.¹¹

We will use Figure 1 to demonstrate this visually.

Figure 1: Schematic of tomatoes and cells undergoing oxidative stress over time (drawn using Inkscape)

Take the tomato as seen in Figure 1, or an apple or any fruit/vegetable. The fruit/vegetable becomes oxidised over time, as it is exposed to oxygen, and so it starts to degrade and become all mushy and a bit gross.

Cells, when exposed to free radicals, work in the same way. Cells can become attacked by free radicals and oxidants over time, which can develop into oxidative stress, which then damages or destroys the cell.

Oxidative stress causes and consequences

Many potential causes of oxidative stress can lead to different diseases, which can team up and together contribute to and collaborate with oxidative stress to cause diseases. ^1,5,9,12 

These causes include:

• Environmental Pollution
• Smoking and tobacco usage
• Ultraviolet (UV) Radiation & Sun Exposure 
• Excessive alcohol use
• Chronic Stress
• Radiation
• Medication
• Chemicals - Certain Pesticides & Industrial Chemicals

Similar to ROS, oxidative stress and damaged cells lead to all manner of health problems, including but not limited to:¹³

• Cancer
• Alzheimer’s Disease
• Diabetes
• Asthma
• Metabolic Disorders
• Heart conditions and diseases
• Infertility in people assigned Male at birth

In this article, we will be addressing oxidative stress and ROS in regards to infertility in people assigned male at birth (AMAB).

Male factor infertility

Infertility is when a couple are unable to become pregnant despite having regular unprotected sex after 12 or more months. There are many factors that could contribute to why a couple might be infertile, such as emotional, social, and physical challenges, as well as sexually transmitted infections (STIs) and problems within certain organs.^12,14

This condition affects millions of couples worldwide, with about half of all infertility cases linked with ‘male factor’ infertility, which affects people assigned AMAB.^15,17

Male factor infertility is usually caused by problems with both sperm and semen. You might be wondering, aren’t they the same thing?

Whilst they often get confused, they are not the same thing:

Semen - Short for seminal fluid, semen is a whitish-grey substance that contains sperm as well as other fluids that help nourish, protect and transport sperm

Sperm - Short for Spermatozoa, a tiny, tadpole-like male reproductive sex cell that joins with a female sex cell to begin fetal development 

Male factor infertility is characterized by low sperm count, poor sperm shape and movement and poor semen quality. ¹⁸

Many studies have suggested that Oxidative Stress could be a new emerging factor in cases of unexplained male infertility relating to sperm and semen.¹⁹

The effect of ROS on sperm

As we have already established, oxidative stress is caused by a build-up of excess ROS, which itself is an imbalance of antioxidants and free radicals, all of which are vital to many biological processes. ROS does not discriminate and affects sperm as well, which has been found to disrupt sperm maturation, sperm function and sperm movement.^19,20

Studies have shown that high levels of ROS cause harmful effects in sperm, resulting in changes to the sperm’s shape and properties that make fertilisation less likely to occur, essentially damaging the sperm.²⁰

The main source of oxidative stress in semen is mostly due to an unusually high number of white blood cells within sperm, a condition known as Pyospermia, as they produce 1,000x more ROS than sperm.²¹

Pyospermia 

Pyospermia is defined as when there are more than 1 million round cells per millilitre of semen and is diagnosed through a test, which shows more than 1 million white blood cells per millilitre.²²

This test uses a Peroxidase dye. Peroxidases are enzymes that help speed up chemical reactions using the unpaired electrons in the free radicals that stain the white blood cells so they 

can be seen in a microscope and counted.²¹ 

White blood cells are important as they help the body’s immune system fight infections and other diseases. Therefore, if you have a large number of white blood cells, it generally means you may have an infection, injury or something else that is harming your body, which could result in Pyospermia.²³

Pyospermia causes and consequences

Pyospermia has several risk factors, with possible causes that include:^24,25

• Infections - General, Urogenital, Genital and Sexually Transmitted
• Inflammation of the urethra and/or prostate
• Pelvic Injuries
• Autoimmune Diseases
• Tobacco, marijuana and alcohol use
• Swollen veins in the scrotum

Studies have shown that there were higher levels of white blood cells in people with infertility compared to healthy controls, which correlated to a lower sperm count, reduced movement and sperm structure.²⁶

From this study, further research supported this, stating that an excess of white blood cells in semen contributed to sperm ROS production, resulting in lower semen quality and damage to sperm DNA.^27,28 Another interesting result from these studies is that lower white blood cell concentrations contribute towards lower levels of oxidative stress, and higher white blood cell concentrations showed greater oxidative stress levels, which suggests that semen white blood cell removal could be useful to reduce oxidative stress.^28,29

Overall, increased ROS levels lead to oxidative stress, which can cause cell damage and/or cell death. Within sperm, high ROS levels result from Pyospermia, which can cause sperm damage and reduced semen quality, which can result in male factor infertility.

How to prevent Pyospermia?

If you are AMAB and are worried about Pyospermia and its implications for infertility and are generally healthy, there are many ways you can reduce your risk of developing Pyospermia:

• Practice safe sex: Reduce your risk of STIs by wearing condoms, avoiding sex if you suspect a partner might have an STI and getting tested regularly
• Avoid injury to your pelvic region
• Avoid tobacco and marijuana products
• Reduce Alcohol Use

Whilst it may not completely eliminate your risk of developing Pyospermia, being in general good health and participating in the prevention methods will help reduce your white blood cell count, therefore reducing the risk of developing oxidative stress in your sperm.

How to prevent Oxidative Stress in general?

If you are someone who wants to avoid oxidative stress-related diseases, not just Pyospermia, there are several prevention methods, such as:^1,5,9,11,30

Consuming more antioxidant-rich food - such as:

• Vitamin C: Citrus fruits (oranges & grapefruits), kiwis, strawberries & peppers
• Vitamin E: Nuts (almonds, peanuts & hazelnuts), spinach & broccoli
• Selenium: Seafood (tuna & salmon), eggs, whole-grain foods (rice, pasta, & bread)
• Beta Carotene: Carrots, apricots, mangoes, melons, sweet potatoes & kale

Quit smoking - Stopping smoking is the best way to prevent oxidative stress, as well as many other diseases

Stress less - High stress levels are associated with oxidative stress, so having fewer life stressors will benefit you

Regular Exercise - Frequent physical exercise does have anti-oxidant effects in addition to general health benefits

Regularly wear suncream - Wearing suncream often protects your skin not just from sunburns but also oxidative stress, without missing out on fun in the sun!

Drink less alcohol - Reducing alcohol intake also prevents many diseases in addition to preventing oxidative stress

Caution with medications and chemicals - Avoid unnecessary radiation and chemical exposure by checking medications and chemicals to reduce contamination risks

Whilst it’s nearly impossible to completely avoid free radical exposure, especially when it comes to environmental factors, taking precautions and all the measures above will greatly reduce your risk of developing oxidative stress.