Surprise! 'Bad' Sperm Get Damaged in Trip to Ejaculation

Startling study finds that the DNA in sperm from the testicles of infertile men is better quality than sperm from their ejaculate

Illustration of human gametes
JESPER KLAUSEN / SCIENCE PHOTO L

Male infertility is a growing problem in the west, and the reasons suggested are many and myriad, from smoking to cellphones to skinny jeans. Sex hadn’t been on the list but, in a sense, maybe it should be. Groundbreaking if preliminary research described over the weekend at the 34th conference of the European Association of Urology reached an unexpected conclusion: Much damage to the genes in sperm cells is happening between the point of their manufacture in the testicle to the point of ejaculation.

The DNA in sperm from the testicles of infertile men is better quality than sperm from their ejaculate, sums up Prof. Sheena Lewis, emeritus of Queens University Belfast, whose company ExamenLab had been involved in the study.

Sperm is manufactured in seminiferous tubules inside the testicles. When one orders ox balls at oriental restaurants in the Middle East, what one is eating is basically flame-grilled seminiferous tubules on a skewer and no, they won’t make one more fertile.

Even when not being served with dipping sauce, the unhappy testicle certainly has been up against it in the modern age. Sperm face challenges, some environmental such as pesticides, some involving lifestyle (sedentary plus laptop). Doctors usually can’t tell a given man what exactly caused his specific shortcoming, but clearly much male infertility stems from damage to the sperm’s DNA. The questions are when, where and why that damage happens.

A lot of people want to know. In the west, around 15% of couples are deemed infertile, meaning that after a year of unassisted endeavor, pregnancy did not ensue.

A third of the cases are due to male infertility and another third is due to female infertility. The last third is due to unknown causes: Male fertility can be impaired by congenital or acquired urogenital abnormalities, cancer, infection, increased scrotal temperature and more.

So a group of English scientists took 63 infertile men and compared the men’s sperm extracted from the testicles before undergoing the ordeal of travel and ejaculation, with their sperm after ejaculation.

They also compared the infertile men’s sperm before and after ejaculation, with the sperm of 76 fertile men.

Unsurprisingly, a greater proportion of the unfertile men had damaged sperm DNA (40%) compared with the fertile men (15%). Okay.

Looking only at the infertile men: Theoretically, the degree of genetic damage to the sperm before and after ejaculation should be the same, right? It’s the same guy – all he did is reach orgasm. But surprisingly, the degree of genetic damage was not the same. 

Cross-section of a testicle
National Cancer Institute / Nat

The shocker was that the extent of DNA damage among pre-ejaculate sperm of the infertile men was comparable to that of the fertile men – around 15% of the men.

“When we looked at sperm taken directly from the testicles of infertile men, we found that it was of similar quality to that of ejaculated, fertile sperm,” said Jonathan Ramsay, a consultant urologist at the Imperial College, London, who had been involved in the research.

Note well that this study does not purport to study all male infertility; nor does it suggest that most male infertility is due to DNA damage. What it shows is where this DNA damage happens, when it does.

What is “attacking” the hapless spermatozoa as they swim through the man’s privates? Oxygen.

The downside of breathing

Breathing is good. But when our oxygen metabolism goes out of whack, we can enter a state called oxidative stress. Simply, extremely reactive oxygen atoms, or molecules with extremely reactive oxygen groups, are running free in our bloodstream, reacting with our biochemistry. The list of conditions and diseases thought to be caused or exacerbated by oxidative stress starts with cancers, neurodegenerative conditions, chronic fatigue and depression, and heart failure.

DNA is a famously double helix, made of two strands. As the sperm swims through the ducts in the male reproductive system, oxidative stress can cause breaks in its DNA.

“This occurs when the sperm are subjected to poor lifestyle habits such as poor diet, sitting at a laptop all day or smoking. Diseases such as Crohn’s disease and Type 2 Diabetes also cause oxidative stress,” writes the team.

Biochemically speaking, antioxidants “capture” these radicals, though that doesn’t mean that taking pills marked “antioxidant” necessarily benefits one. The USDA also notes the absence of that there is no evidence that antioxidants detected in our food translate into an antioxidant effect in the body.

The bottom line of this study is that whatever the specific cause of a given infertile man’s condition, extracting sperm directly from the testes, by needle, could possibly improve his chances of procreation. This has yet to be actually proven, but it does follow logically.

There are caveats to this discovery of post-manufacture genetic damage. One: the study was not peer-reviewed. Two: the sample size was very small – 63 infertile men compared with themselves and with a sort of control, of 76 fertile men. Three: Saying “infertility” is like saying “apparel” or “nematode” – the specific case can be within a vast potential range. And finally, the results of the study still bear reproduction.

Sir Freddie,  one of the original semen donors, in 1968. He lived with the Walker family.
\ the Walker family

Counting sheep

In happier news of sperm, separate researchers at the University of Sydney reported that the “world’s oldest sperm” proved to be perfectly fine. The reference turned out to be sperm from rams frozen 50 years ago in Sydney, Australia, specifically in 1968. Their lab electricity system must be very reliable.

The long and short is that after half a century of storage in liquid nitrogen, scientists thawed the seed, did what they did and lo and behold, of the 56 Merino ewes they artificially inseminated, 34 became pregnant.

Their rate of live lamb birth was as high as with sperm frozen for just 12 months, reported the team, which was funded in part by Australian Wool Innovation.

If anything it was slightly better – the success rate with seed of the original donors was 61%, compared with 59% for the latter-day males.

For what it’s worth, the 50-year old sperm came from four rams owned by the Walker farming family. One of the rams had been named Sir Freddie. He had been born in 1963. Now you know.

To us who do not farm sheep for their wool, it is amusing to note that when testing the sperm, the scientists managed to produce a throwback, presumably unintentionally.

“The lambs appear to display the body wrinkle that was common in Merinos in the middle of last century, a feature originally selected to maximize skin surface area and wool yields. That style of Merino has since largely fallen from favor as the folds led to difficulties in shearing and increased risk of fly strike,” explained associate professor Simon de Graaf of the University of Sydney.

Sheep semen thawed after 50 years under a microscope.
University of Sydney