April 5, 2024

NIH awards $3.4M to School of Medicine to investigate biomarkers for better reproductive success

The laboratory members of J. Richard Pilsner, Ph.D., M.P.H., center, will use the new National Institutes of Health award to examine mitochondrial DNA levels in sperm.

The diagnosis of male fertility has not changed in decades and primarily relies on conventional semen parameter analyses such as sperm count, motility and morphology, which are poor predictors of couples’ reproductive success.

A new $3.4 million award to the Wayne State University School of Medicine from the National Institutes of Health aims to overcome the limitations of conventional semen analyses by examining mitochondrial DNA levels in sperm as a novel biomarker of sperm fitness and predictor of couples’ reproductive success.

The project will be led by School of Medicine Professor of Obstetrics and Gynecology J. Richard Pilsner, Ph.D., M.P.H.

Professor of Obstetrics and Gynecology J. Richard Pilsner, Ph.D., M.P.H.

“We know that the mitochondrial genome is inherited maternally. As such, this award will build on our previous research that has shown that men with higher levels of mitochondrial DNA in sperm have lower pregnancy success with their partner,” Dr. Pilsner said.

The grant, from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, is expected to support the project, “Sperm mitochondrial biomarkers and male reproductive health,” through January 2029.

“Given the limitations of conventional semen analysis, our research is highly significant for its potential to positively impact clinical care by novel measurements of sperm fitness predicting couples’ reproductive success and is the first step toward developing interventions for improve male fertility,” Dr. Pilsner added. “Traditionally, the burden of a successful pregnancy fell largely on the female partner. We now recognize that the male partner contributes not only DNA at fertilization but also other factors that impact early-life development, and ultimately reproductive success.”

Dr. Pilsner is associate director of the C.S. Mott Center for Human Growth and Development and the Robert J. Sokol, M.D., Endowed Chair of Molecular Obstetrics and Gynecology.

The Pilsner laboratory’s research to date suggests that sperm mitochondrial DNA copy number (mtDNAcn) and deletions (mtDNAdel) may fill this gap, and directly measure the physiological processes that determine male reproductive health.

The team’s published data suggest that mtDNA biomarkers are related to male infertility, fertilization probability, clinical infertility treatment outcomes and time-to-pregnancy. In the new project, the researchers will evaluate these potential relations in large study samples. While conventional semen parameters remain controversial in predicting male factor infertility and reproductive success, little is known about how best to leverage the combination of semen parameter and novel mtDNA biomarker data to advance clinical care to understand the male contribution to reproductive success.

They will evaluate these relationships using data and biospecimens from the NIH-funded Folic Acid and Zinc Supplementation Trial, or FAZST and the Sperm Environmental Epigenetics and Development Study, or SEEDS.

“Using these resources, we can evaluate hypotheses in a large (n=2,570) preconception cohort that includes couples using a range of fertility treatments and provide opportunity to test mechanistic pathways,” Dr. Pilsner said.

“This project is an excellent example of promising research that may improve our understanding of a complex health issue many people face,” said Ezemenari M. Obasi, Ph.D., vice president for research at Wayne State University. “Dr. Pilsner and his research team’s work will offer enhanced understanding of the reproductive health of males, but also may one day lead to new treatments to reverse male infertility.”

The project number for this Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health award is R01HD110462.

For more information on the work, visit www.pilsnerlab.com

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