Study Offers Insight into Combating Male Infertility

Researchers from the Guangzhou Women and Children’s Medical Center in China published a study this week in the medical journal Development, offering new insight into preventing infertility in men. 

Currently, at least 30 million men worldwide are infertile, and one in seven couples are considered clinically infertile, or unable to achieve pregnancy after one year of having intercourse without using birth control.

For about half of all cases, the cause of male infertility cannot be determined, but what is known is that a complete lack of sperm occurs in about 10% to 15% of men who are infertile, and that pre-existing conditions like having cancer and undergoing chemotherapy or radiation treatments can damage sperm. 

Infertility in men often occurs in the tail of the sperm, called the flagellum, which creates mobility to push the sperm towards the egg, allowing travel through the sticky medium of the human body before meeting the egg. 

The mitochondria propels the sperm to move towards the egg, and when the sperm is near the egg it releases an enzyme to break down the exterior lining to fertilize it. 

However, infertility causes the fibrous sheath which covers the tail of the sperm to be affected. Animals who swim through water, such as fish, do not have this protein, called FSIP2 or if they do it is defective, because fertilization occurs outside of the body.

To study the causes of male infertility and how to address them, researchers collected samples of sperm from infertile men, including a sample from a man with a malformed flagellum. 

Seeking to understand the function of the FSIP2 protein, researchers developed two study groups using mice, one group was recreated using the FSIP2 mutation of the human patient with infertility, and the second group was created using a mutation from animals which overproduce FSIP2 protein. 

Half of the mice who received the protein mutation from the human patient with infertility could not swim forward, although their sperm tail was still able to move. 

However, the group of mice who received the overproduced FSIP2 protein, remained fertile, and had over seven times more “super-long sperm,” meaning the mice were more fertile and more capable of fertilizing an egg when compared to the mice that received the FSIP2 mutation from the human patient. 

Researchers discovered that the outcomes in mice who received the protein mutation from the human patient were vastly different from the mice receiving the overproduced FSIP2 due to the fact there was not enough protein to cover the sheath, mitochondria, and acrosomal vesicles. 

This absence of protein was not seen in the mice overproducing FSIP2, and instead the sheath was extremely fibrous allowing sperm to be more mobile.

“There are thousands of genes involved in the fertility process, and these genes show up often times as flagella proteins, which can have far reaching benefits beyond the development of tail sperm,” said Dr. Amin Herati, director of Male Infertility and Urologist at the Brady Urological Institute at Johns Hopkins. 

Herati, whose research focuses on tail sperm proteins, said reasons for changes in fertility are also largely environmental, as many individuals are exposed to endocrine disruptor agents, or natural or synthetic chemical substances which can interfere with the endocrine system, on a day-to-day basis. 

These chemicals are often found in common products like disinfecting wipes, and consistent exposure has proven to disrupt sperm production and quality in humans and animals.

“In some cases, we find that the problem rests with hormone deficiency, and when we boost the hormone levels their fertility will increase, or if they have anatomic problems, like varicocele veins, when we fix those veins in a large number of men about 60-70% will have significantly improved semen parameters,” said Herati. 

“But to say we reversed their fertility, that number is harder to quantify, because there are two people involved and the problem is multi-factorial even within each patient,” he continued. 

Typical courses of treatment for male infertility often involve invasive procedures, including surgery to repair the varicocele, an enlargement of the veins within the loose bag of skin that holds testicles, or to retrieve sperm directly from testicles if no sperm are present in ejaculate.

Assisted reproductive technologies are also invasive, as they involve obtaining sperm through normal ejaculation, or surgical extraction from the donor, and inserting those sperm into the female genital tract, or through methods like in vitro fertilization, or intracytoplasmic sperm injection. 

“In some cases, where there are tail abnormalities, rather than sperm swimming to the egg, they can artificially inject the sperm directly into the egg,” said Herati.

Medications and hormone replacements, as well as counseling, have also been known to help to improve fertility in cases where men have erectile dysfunction, or premature ejaculation.

There are also herbs or supplements known to help increase male fertility, such as Folic acid and zinc combinations, Selenium, Vitamin C, and Vitamin E, although none of these natural remedies are able to treat the specific underlying causes of the disorder. 

While male infertility can impact reproductive outcomes, it can also increase the risk of testicular cancer, melanoma, colon cancer, and prostate cancer, and lead to mental health conditions like depression for men who may experience stress in their relationships from inability to have a child.

The study offers insight into the possible creation of new treatments to address restoring movement of the sperm tail, and as Herati said, even preventing the mutation which causes infertility in men. 

“Having that awareness they have a hormone abnormality or potential genetic problem would be something to pop-up much earlier, rather than further down the road,” said Herati.