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Elevated Levels of Defective Mitochondrial DNA Predict Likelihood of Reproductive Success

By LabMedica International staff writers
Posted on 14 Oct 2020
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Image: Mitochondrial DNA comprises the small circular chromosome found inside mitochondria. The mitochondria, and thus mitochondrial DNA, are passed from mother to offspring (Photo courtesy of Wikimedia Commons)
Image: Mitochondrial DNA comprises the small circular chromosome found inside mitochondria. The mitochondria, and thus mitochondrial DNA, are passed from mother to offspring (Photo courtesy of Wikimedia Commons)
A sperm biomarker has been found that may be able to supplement or replace the semen parameters that poorly predict reproductive success yet are the most prevalent diagnostic tool for male infertility.

Mitochondrial DNA is maternally inherited, and sperm mitochondrial DNA copy number (mtDNAcn) typically decreases eight-to-10 fold during spermatogenesis to ensure that it is low upon fertilization. Previous studies have shown that elevated sperm mitochondrial mtDNAcn and mitochondrial DNA deletions (mtDNAdel) were associated with decreased semen quality and lowered the odds of fertilization in men seeking fertility treatment.

To confirm this association, investigators at the University of Massachusetts Amherst (USA) determined sperm mtDNAcn and mtDNAdel from 384 semen samples using triplex probe-based quantitative PCR. Probability of pregnancy within one year was compared by mitochondrial DNA.

Results revealed that men with higher sperm mtDNAcn had as much as 50% lower odds of cycle-specific pregnancy and 18% lower probability of pregnancy within 12 months. The investigators stressed that the population examined in this study consisted primarily of Caucasian men and women and thus large diverse cohorts would be necessary to confirm the associations between sperm mtDNAcn and couple pregnancy success in other races/ethnicities.

"Clinically, the diagnosis of male infertility really has not changed in decades," said senior author Dr. Richard Pilsner, associate professor of public health and health sciences at the University of Massachusetts Amherst. "In the last 10 to 20 years, there have been major advances in the understanding of the molecular and cellular functions of sperm, but the clinical diagnosis has not changed or caught up. Understanding what is causing the retention of mitochondrial copy number during spermatogenesis will help us come up with better platforms to intervene and to promote better reproductive success. The logical next step was to determine if the associations between sperm mitochondrial biomarkers and fertilization among couples seeking infertility treatment could be extended to couples from the general population,"

The mitochondrial DNA study was published in the October 6, 2020, online edition of the journal Human Reproduction.

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University of Massachusetts Amherst

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