Scientists at the University of Massachusetts Amherst say a discovery could lead to a better diagnosis of male infertility.
Researchers at the University of Massachusetts Amherst have identified a single-measure biomarker in sperm mitochondria DNA this can predict male reproductive health and pregnancy success.
The discovery applies not only to couples caring for infertility, but to the general population as well. This biomarker could become a more accurate predictor of male infertility than semen parameters that health organizations and clinicians have long relied on.
“Clinically, the diagnosis of male infertility has not really changed for decades,” says UMass Amherst environmental epigeneticist Richard Pilsner, corresponding author of the study published today, October 6, 2020 in the journal Human reproduction. “Much advances have been made in understanding the molecular and cellular functions of sperm over the past 10 to 20 years, but the clinical diagnosis has not changed or caught up.”
In addition to Pilsner, the UMass research team also included the main author Allyson Rosati, who wrote the thesis as part of her thesis and recently completed a master’s degree in molecular and cell biology. Brian Whitcomb, Associate Professor of Epidemiology in the School of Public Health and Health Sciences. They worked with reproductive and perinatal epidemiologist Germaine Buck Louis, Dean of the College of Health and Human Services at George Mason University, and Sunni Mumford and Enrique Schisterman at the National Institute of Child Health & Human Development.
“This project is a really nice example of interdisciplinary work and team science,” says Whitcomb. “This research required the measurement of biomarkers in the laboratory in combination with statistical modeling. Answering such scientific questions benefits from a wide range of specialist knowledge. ”
Mitochondrial DNA is maternally inherited, and sperm mitochondrial DNA copy number (mtDNAcn) typically decreases eight to ten fold during spermatogenesis to ensure that it is low at fertilization. In previous research by Pilsner, Whitcomb, and others, increased mtDNAcn and mitochondrial DNA deletions (mtDNAdel) were associated with decreased semen quality and a lower chance of fertilization in men seeking fertility treatment.
“The next logical step was to determine whether the associations between mitochondrial sperm biomarkers and fertilization could be extended to couples in the general population in couples seeking infertility treatment,” says Pilsner.
Researchers accessed sperm samples from the Longitudinal Investigation of Fertility and the Environment (LIFE) study, which recruited 501 couples from Michigan and Texas from 2005 to 2009 to examine the relationships between lifestyle, including environmental chemicals, and human fertility .
They assessed sperm mtDNAcn and mtDNAdel from 384 semen samples and analyzed their relationship with the probability of pregnancy within one year. They found that men with higher sperm mtDNAcn had a 50% lower chance of cycle-specific pregnancy and an 18% lower chance of pregnancy within 12 months.
“Remarkably, we saw a strong inverse association between mitochondrial sperm biomarkers and the time to pregnancy of couples,” says Pilsner.
Whitcomb adds, “Mitochondrial DNA in sperm appears to reflect an underlying physiological phenomenon that affects sperm function.”
More research is needed to further investigate the effects of changes in mtDNAcn and mtDNAdel due to defective mitochondria or damaged mtDNA. “We need to use our understanding of the molecular toolkit to develop a better predictor of male fertility and fertility,” says Pilsner.
A next step is to study the factors that mediate the changes in the mitochondrial DNA of the sperm. They could contain environmental toxins or other causes of inflammation and oxidative stress, the scientists said.
“If we understand what causes the retention of mitochondrial copy number during spermatogenesis, we can find better platforms to intervene and promote better reproductive success,” says Pilsner.
Reference: “Sperm Mitochondrial DNA Biomarkers and Couple Fertility” by Allyson J. Rosati, BS, Brian W. Whitcomb, Ph.D., Nicole Brandon, MS, Germaine M. Buck, Louis Ph.D., Sunni L. Mumford , Ph. D., Enrique F. Schisterman, Ph.D. and J. Richard Pilsner, Ph.D., October 6, 2020, Human reproduction.