Researchers at the University of Massachusetts Amherst have identified a
single-measure biomarker in sperm mitochondrial DNA that may predict male
reproductive health and pregnancy success.
The discovery applies not just to couples seeking care for infertility but
also for the general population. This biomarker could become a more accurate
predictor of male infertility than semen parameters, on which health care
organizations and clinicians have long relied.
"Clinically, the diagnosis of male infertility really hasn't changed in
decades," says UMass Amherst environmental epigeneticist Richard Pilsner,
corresponding author of the study published today, Oct. 6, in the journal
Human Reproduction. "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 hasn't changed or caught up."
In addition to Pilsner, the team of UMass researchers included lead author
Allyson Rosati, who wrote the paper as part of her undergraduate honors
thesis and recently completed a master's in molecular and cellular biology;
Brian Whitcomb, associate professor of epidemiology in the School of Public
Health and Health Sciences. They collaborated 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," Whitcomb says. "This research required measurement of biomarkers
in the laboratory combined with statistical modeling. Answering scientific
questions like this one benefits from a broad range of expertise."
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. In previous research by
Pilsner, Whitcomb and others, increased mtDNAcn and mitochondrial DNA
deletions (mtDNAdel) were associated with decreased semen quality and lower
odds of fertilization in men seeking fertility treatment.
"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," Pilsner
says.
The 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 association with the probability of pregnancy within one year. They
found 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.
"Remarkably, we saw a strong inverse association between sperm mitochondrial
biomarkers and couples' time-to-pregnancy," Pilsner says.
Adds Whitcomb, "Mitochondrial DNA in sperm seems to reflect some underlying
physiological phenomenon that affects sperm function."
More research is needed to further examine the impact of changes in mtDNAcn
and mtDNAdel, which may result from defective mitochondria or damaged mtDNA.
"We need to take advantage of our understanding of the molecular toolkit
that we have to develop a better predictor of male fertility, as well as
fecundability," Pilsner says.
A next step is to examine the factors mediating the changes in sperm
mitochondrial DNA. They could include environmental toxins or other causes
of inflammation and oxidative stress, the scientists hypothesize.
"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," Pilsner says.
Reference:
Mackens S, Mostinckx L, Drakopoulos P, et al. Early pregnancy loss in
patients with polycystic ovary syndrome after IVM versus standard ovarian
stimulation for IVF/ICSI. Mol. Hum. Reprod. 2020. doi:
10.1093/humrep/deaa200
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