Causes of Teratozoospermia

Causes of Teratozoospermia

Known causes of teratozoospermia include:

• Genetic defects
• Hormone imbalance
• Varicoceles
• Infection
• Obesity
• Smoking
• Drugs and alcohol
• Overheating testicles
• Chemicals and heavy metals

Genetic Defects

Genetic defects are a known cause of poor sperm morphology. Specifically, any defects (or mutations) in the following genes:

• AK7 (multiple morphological abnormalities of the flagella)
• ARMC2 (multiple morphological abnormalities of the flagella)
• AURKC (macrozoospermia)
• BSCL2 (lipid dysfunction)
• CCDC62 (globozoospermia)
• CCIN (globozoospermia)
• CFAP43, CFAP44, CFAP47, CFAP69, CFAP251 (multiple morphological abnormalities of the flagella)
• DNAH1, DNAH6, DNAH11 (multiple morphological abnormalities of the flagella)
• DPY19L2 (globozoospermia)
• FSIP2 (multiple morphological abnormalities of the flagella)
• PICK1 (globozoospermia)
• PMFBP1 (globozoospermia)
• SPATA6, SPATA16 (globozoospermia)
• SUN5 (globozoospermia)
• TENT5D (multiple morphological abnormalities)
• ZPBP1 (globozoospermia)

Hormone Imbalance

Teratozoospermia could be due to a result of a defect during sperm maturation. It is known that the hormone testosterone is responsible for the later stages of spermatogenesis and if it is in low concentration, this could lead to defective sperm cells.

While males with severe teratozoospermia display altered LH and FSH hormone levels compared to other infertile males with normal sperm morphology above 4%.
_{Source: Kovac J R, et al. (2016)}

Varicoceles

Studies consistently show that males diagnosed with varicoceles have significantly worse semen parameters including normal morphology.
_{Source: Azab S S, et al. (2021); Finelli R, et al. (2021); Gill K, et al. (2021); Morini D, et al. (2021)}

A varicocele is the enlargement of veins responsible for the drainage of blood from the testicles. This usually affects both testicles so it’s important health practitioners utilise sensitive imaging techniques.

Unfortunately, the underlying cause of varicoceles is not yet known however experts suggest that scrotal hyperthermia, oxidative stress, hormonal disturbances, testicular hypoperfusion, testicular hypoxia or backflow of toxic substances may cause varicocele.

Infection

Up to 35% of male infertility cases are associated with urogenital system infections. These infections and related disorders (incl. bacteriospermia, leukocytospermia, orchitis) can impair the production of sperm, reduce sperm quality, increase semen viscosity (hyperviscosity) or pH, and cause scarring which blocks sperm movement. Infection of the epididymis, testicles and STIs such as chlamydia trachomatis, human papillomavirus, ureaplasma urealyticum, trichomonas vaginalis and mycoplasma genitalium are some examples linked to low sperm morphology.
_{Source: Xianchun F, et al. (2023); Pérez-Soto E, et al. (2022); Volz Y, et al. (2022); Eini F, et al. (2021); Liu K S, et al. (2021); Pérez-Soto E, et al. (2021); Yasynetskyi M, et al. (2021); Lampiao and Chisaka, (2020); Masarani M, et al. (2006); Moulik S, et al. (1989)}

Obesity

The link between obesity and teratozoospermia or even other sperm parameters remains the subject of debate among researchers. While some believe that the high prevalence of obesity explains the general decline in sperm parameters in our modern world, a proven relationship remains elusive. As of now, researchers believe there are 3 main pathways that potentially explain the link between high BMI and abnormal sperm parameters:

1. Obesity causes a decrease in the secretion of androgen (i.e. testosterone) and an increase in estrogen levels
2. Oxidative stress at the testicular level affects spermatogenesis
3. Accumulation of fat tissue in the pubic and inner thigh region may cause above average scrotal temperature

Interestingly, two of the largest studies to date suggest that in fact only older men (>40) who are obese have impaired semen quality, including worse sperm morphology, compared to older men with normal BMI (<25kg/m²).
_{Source: Pino V, et al. (2020); Veron G L, et al. (2018); Anderson J M, et al,. (2015); Tsao C W, et al. (2015); Du Plessis S S, et al. (2010); Chavarro J E, et al. (2009)}

Smoking

Smoking tobacco has been shown to affect the quality of sperm, relative to the quantity and duration of smoking. Smoking also significantly alters hormone levels and trace minerals in the body, however its effect on sperm morphology is small. Smoking’s mechanism of action includes an increase in oxidative stress via nitrogen oxide synthase, impaired energy supply in sperm mitochondria due to reduced fatty acid uptake, altered tetrahydrobiopterin biosynthesis and increased sperm apoptosis. Overall, smoking impacts all sperm parameters and is unlikely to be a cause of isolated teratozoospermia.
_{Source: Bazid H, et al. (2021); Engel K M, et al. (2021); Blay R M, et al. (2020); Bundhun P K, et al. (2019); Rehman R, et al. (2019); Taha E A, et al. (2012)}

Drugs and Alcohol

Recreational drugs such as cocaine, methamphetamine and marijuana can reduce both the quality and quantity of sperm to varying degrees.

Cocaine use alters various hormones and has a toxic effect on spermatogenesis, however it has not been linked to isolated cases of teratozoospermia.

Methamphetamine significantly interferes with spermatogenesis via multiple pathways, leading to decreased sperm count, motility and morphology in animal studies.

Meanwhile marijuana users are 2.15 times as likely to have abnormal strict morphology, and 2.8 times as likely to display abnormal semen volume. Marijuana use specifically decreases testosterone and LH levels while increasing FSH, with long-term consequences related to dose and duration.

Lastly, alcohol consumption lowers testosterone levels and negatively affects spermatogenesis if chronic (long-term regular habit). Moderate alcohol intake causes a significant decrease in semen volume, and a minor decrease in normal sperm morphology (-2%).

Overheating Testicles

Most experts agree that elevated scrotal temperature impairs sperm production. In mammals, the testicles are found outside the body, keeping the scrotal temperature 2-8°C lower than core body temperature (37°C). Mild scrotal heat stress eliminates the spermatogonial germ cells in the seminiferous tubules causing a reduction in sperm density and morphological changes within the tissue. Cells that survive hyperthermia usually develop into morphologically abnormal and poorly motile spermatozoa leading to oligoasthenoteratozoospermia but not teratozoospermia.

Chemicals and Heavy Metals

Long term exposure to industrial chemicals, metals, pesticides, insecticides and air pollution also contributes to male infertility via reduced sperm quality, including the percentage of sperm with normal morphology. Unfortunately, research in this field is generally reactive and not proactive, meaning the list below will never be a complete guide.

For males with significantly impaired sperm quality, a general audit of the home and work environment is good practice to identify any potentially toxic substances.