Professor and Robert J Sokol, MD Endowed Chair of Molecular Obstetrics and Gynecology Director of Molecular Genetics and Infertility | C.S. Mott Center for Human Growth and Development Department of Obstetrics and Gynecology | Wayne State University School of Medicine Center for Urban Responses to Environmental Stressors (CURES P30)| Institute of Environmental Health Sciences
C.S. Mott Center
Department of Obstetrics & Gynecology
Wayne State University
School of Medicine
275 East Hancock; Room 297
Detroit, MI 48201
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.
Learn more about the Pilsner lab and research opportunities available at: www.pilsnerlab.com
Oluwayiose OA, Marcho C, Wu H, Houle E, Krawetz SA, Suvorov A, Mager J, Pilsner JR. Paternal preconception phthalate exposure alters sperm methylome and embryonic programming. Environmental International. 2021 Oct (155) 106693.
Marcho C, Oluwayiose OA, Pilsner JR. The preconception environment and sperm epigenetics. Andrology. 2020 Jul;8(4):924-942.
Oluwayiose OA, Josyula S, Houle E, Marcho C, Brian W Whitcomb, Rahil T, Sites CK, Pilsner JR. Association between sperm mitochondarial DNA copy number and nuclear DNA methylation.
Epigenomics. 2020 Dec;12(24):2141-2153.
Oluwayiose OA, Wu H, Saddiki H, Whitcomb BW, Balzer LB, Brandon N, Suvorov A, Tayyab R, Sites CK, Hill L, Marcho C, Pilsner JR. Sperm DNA methylation mediates the association of male age on reproductive outcomes among couples undergoing infertility treatment. Sci Rep. 2021 Feb 5;11(1):3216.
Rosati AJ, Whitcomb BW, Brandon N, Buck Louis GM, Mumford SL, Schisterman EF, Pilsner JR. Sperm
mitochondrial DNA biomarkers and couplef fecundity. Hum Reprod. 2020 Nov 1;35(11):2619-2625.
Wu H, Whitcomb BW, Huffman A, Brandon N, Labrie S, Tougias E, Lynch K, Rahil T, Sites CK, Pilsner JR. Associations of sperm mitochondrial DNA copy number and deletion rate with fertilization and embryo development in a clinical setting. Hum Reprod. 2019 Jan 1;34(1):163-170.
Wu H, Huffman AM, Whitcomb BW, Josyula S, Labrie S, Tougias E, Rahil T, Sites CK, Pilsner JR. Sperm mitochondrial DNA measures and semen parameters among men undergoing fertility treatment. Reprod Biomed Online. 2019 Jan;38(1):66-75.
Wu H, Ashcraft L, Whitcomb BW, Rahil T, Tougais E, Sites CK, Pilsner, JR. Parental contributions to early embryo development: influences of urinary phthalate and phthalate alternatives among couples undergoing in-vitro fertilization treatment. Hum Reprod. 2017 Jan;32(1):65-75.
Wu H, Estill M, Shershebnev A, Suvorov A, Krawetz SA, Whitcomb BW, Sites C, Rahil T, and Pilsner JR. Preconception Urinary Phthalate Concentrations and Sperm DNA Methylation Profiles among Men Undergoing IVF Treatment. Hum Reprod. 2017 Nov 1;32(11):2159-2169.
Pilsner JR, Shershebnev A, Medvedeva YA, Suvorov A, Wu H, ….. Hauser R, Sergeyev O. Peripubertal serum dioxin concentrations and subsequent sperm methylome profiles of young Russian adults. Reprod Toxicol. 2018 Mar 14;78:40-49.
Wu H, de Gannes M, Luchetti G, Pilsner JR. Rapid Method for the Isolation of Mammalian Sperm DNA. Biotechniques June 2015; 58(6):293-300.14;78:40-49.