Research in Focus

Spermatozoa have been traditionally viewed as vehicles for the delivery of only the paternal genome to oocytes upon fertilization.  In this context, paternal contributions to offspring phenotype are strictly limited to germline genetic information without the ability to impart environmental information that is encountered during the life course. However, a growing body of compelling data from our lab (and others) demonstrates that environmental exposures can be embodied within the developing male germ cell without altering the germline genetic information and, in turn, can affect the offspring phenotype, indicating that additional pathways allow the transfer of environmental information from sperm to oocytes.

Figure 1: Windows of susceptibility during male germ cell development. ( Pubmed )

Figure 1: Windows of susceptibility during male germ cell development. (Pubmed)

In humans, male germs cells do not attain reproductive capacity until the second decade of life. Despite this long latency period, male germ cells begin development early in fetal life and, upon sex determination, embark on a remarkable journey of cellular differentiation and morphological changes to prepare for its sole purpose—the propagation of its genome.  During development, male germ cells progress from primordial germ cells (PGCs) to diploid spermatogonia and then finally to haploid spermatozoa. To undergo these transformations, stage-specific epigenetic reprogramming is required - each of these reprogramming events represent windows of susceptibility in which environmental exposures can sculpt the epigenetic landscape of sperm prior to fertilization.

The Pilsner lab is currently examining the effects of environmental exposures on the preconception window (Figure 1; Steps 3-5) of male germ cell development known as spermatogenesis, which takes around 74 days (around 35 days in mice) to produce mature haploid spermatozoa from diploid spermatogonia. Thus, epigenetic reprogramming during spermatogenesis in the adult provides a final opportunity for sperm to “epigenetically match” their current environment prior to fertilization. Additionally, we are also investigating the role of sperm mitochondria DNA copy number and deletions as biomarkers for semen quality and reproductive success.

If you are a talented graduate or postdoctoral fellow interested in joining the Pilsner lab, click here.


Current funding

2016-2018    NIH/NIEHS: R21-ES026778

Embryonic inheritance of sperm methylome after adult exposure to phthalates

Role:  Multi-Principal Investigators with Jesse Mager

2017-2022    NIH/NIEHS: R01-ES028214        

Male preconception phthalates and offspring embryo and sperm allele-specific methylome programming

Role: Principal Investigator

2018-2023    NIH/NIEHS:  R01-ES028298       

Paternal preconception phthalates and reproductive health - potential mediation through sperm DNA methylation.

Role: Principal Investigator


Past funding

2014-2017    NIH/NIEHS:  1K22-ES023085-01  

Phthalate Exposure, Sperm DNA Methylation and Early-life Development

Role:  Principal Investigator

2013-2016    NIH/NCI: R15-CA170111-01                                                                                                        

Epigenotyping in Peripheral Blood DNA and Risk of Breast Cancer

Role: Co-Investigator (Principal Investigator: Susan Sturgeon)


2014-2016    Russian Science Foundation: 14-045-00065            

Effects of persistent organic pollutants and endocrine disrupting chemicals on male fertility and epigenetic reprogramming of male germ cells.

Role: Co-investigator/Scientific advisor (Principal Investigator: Oleg Sergeyev)