Researchers from the University of Nevada have come up with a novel potential explanation for why male infertility may occur in some males. Using the male pseudoscorpion as an animal model of study, the scientists discovered that not only can the common antibiotic tetracycline result in decreased fertility via significantly reduced sperm viability, but also that the effect can be passed onto male progeny.
Tetracycline is a broad spectrum antibiotic that has been used for decades in fighting infection, but more recently is used less because of the development of antibiotic resistance in many pathogens. Today, tetracycline is used for treating eye and genital infections caused by chlamydia; in treating bronchitis due to Haemophilus influenza; for infection with Rocky Mountain spotted tick fever and for treating skin acne caused by bacteria that feed on the oils produced by the sebaceous glands.
Tetracycline is typically contraindicated for pregnant and nursing mothers because it has mutagenic properties that can damage a fetus as well as cause permanent teeth staining and bone development problems in growing children.
Tetracycline works by inhibiting protein synthesis in the mitochondria, which not only are involved in creating cellular energy but are also involved in sperm production and sperm motility. Previous animal research studies have shown that exposure of sperm to tetracycline affects mitochondrial function related to sperm morphology, sperm count, sperm motility and sperm viability. Similar results were also seen with human sperm cultured in petri dishes with tetracycline added.
The aim of the study was to determine the effect tetracycline has on fertility and whether its effects go beyond the parent (F0) generation.
In the study three generations of pseudoscorpions were analyzed: the original parent generation (F0), the first progeny generation (F1) and the grand-progeny (F2). The pseudoscorpion species Cordylochernes scorpioides was chosen because its sexual physiology is ideally suited for fertility studies.
The F0 generation consisted of combinations of both tetracycline-treated and untreated (control) males and females to produce 4 cross types in the F1 generation. The F1 generations were then crossed to generate the F2 generation.
What the researchers found was that males in the F1 generation (that had not been exposed to tetracycline directly) experienced decreased sperm viability as seen in the F0 males that had been treated with tetracycline before mating. However, in the F2 generation the grand-progeny males did not shown decreased sperm viability.
"This is the first research to show a transgenerational effect of antibiotics," says David Zeh, Chair of the Department of Biology in the College of Science and a co-author of the study. "Tetracycline has a significant detrimental effect on male reproductive function and sperm viability of pseudoscorpions—reducing viability by up to 25 percent—and now we know that effect is passed on to the next generation. We didn’t see the effect in subsequent generations."
The researchers of the study propose that their results demonstrate that tetracycline may induce epigenetic changes in male reproductive tissues that are then passed onto their male progeny in the F1 generation.
Epigenetic changes are a type of non-genetic cellular memory where a change in phenotype occurs in offspring that is not due to a mutation or other nucleotide change in the organisms' DNA. Rather, that the change is most likely due to a temporary stop or start signal on a particular section of DNA called "DNA methylation" where methyl groups are either added or removed and thereby affect genetic expression.
In the pseudo-scorpion study it may be that the tetracycline is affecting the methylation of the mitochondrial DNA involved in sperm development that is then passed on directly to the F1 generation-but disappears by the F2 generation. The authors, in fact, point out previous studies that have shown multiple instances of epigenetically-based phenotypic disruption that could explain what is occurring in their pseudo-scorpion study.
The significance of their research is that not only does it raise the possibility that some antibiotics may affect fertility, but that it also poses an example of where such effects can be passed onto subsequent generations that were not exposed to an infertility-causing agent. Whether or not this occurs in humans as well remains to be tested, but does raise the question of whether some common antibiotics chemically similar to tetracycline may play a role in some cases of male infertility.