Richard Pilsner

Paternal environmental contributions to reproductive health via sperm epigenetics

The Pilsner lab addresses the interface of environmental epidemiology, toxicology, and reproductive health with a particular emphasis on epigenetic mechanisms. Specifically, our research provides a paternal perspective by delineating the role of sperm epigenetics as a pathway linking paternal preconception environmental exposures to reproductive and offspring health. Such research is critical to understand the paternal environmental determinants of reproductive health, early-life development and future health of offspring. We also recognize that translational research extends from bench-to-bedside, and our current research portfolio echoes this notion with research spanning traditional silos that include both epidemiologic and rodent research. The centerpiece of our research is the environmental health preconception cohort, Sperm Environmental Epigenetics and Development Study (SEEDS), in which we are examining the relationships of preconception phthalates in males on embryo development and live birth. To complement our research goals in humans, we are also conducting experiments in mice to better understand the intergenerational inheritance of the sperm methylome stemming from preconception phthalate exposures. Collectively, the impact of our research aims to facilitate a paradigm shift in the way reproductive success is viewed, such that the burden of environmental health may not be restricted to expectant mothers but rather is equally shared with male partners via sperm epigenetics.

Uncovering novel biomarkers of male infertility and reproductive success

The second arm of research in the Pilsner lab aims to identify novel sperm biomarkers of male infertility and couples’ reproductive success. Male factor infertility is typically determined using measures of semen quality and World Health Organization (WHO) cut points to define abnormality. However, a wealth of data demonstrate that this approach poorly predicts reproductive success and semen parameters have minimal association with fecundability, raising questions about the significance and interpretation of conventional approaches for measuring male infertility. Our published work from SEEDS has shown that sperm mitochondrial DNA copy number (mtDNAcn) is a strong predictor of semen parameters (sperm count, concentration, motility, and morphology) and is also related to fertilization rates. To expand this line of research, our unpublished data in the LIFE Study show that sperm mtDNAcn is strongly related to couples fecundability as measured by time-to-pregnancy. Ongoing research is also developing novel sperm epigenetic clocks (i.e., a proxy of biological aging of sperm) to understand its relationship with reproductive outcomes in an IVF setting as well as in non-clinical populations. We are also pursuing these lines of research utilizing mouse models. Lastly, we are currently examining the role of small non-coding RNA (sncRNA) from extracellular vesicles in human seminal plasma on reproductive success.