Dr. Richard Pilsner, assistant professor of environmental health sciences at the UMass Amherst School of Public Health and Health Sciences, along with Dr. Jesse Mager, associate professor of veterinary & animal sciences at UMass Amherst, recently received a two-year, $375,000 grant from the National Institutes of Health to investigate whether sperm from adult mice exposed to endocrine-disrupting chemicals is linked to health effects in the offspring.
[Photo: Dr. Richard Pilsner]
Drs. Pilsner and Mager will study a high- and low-dose exposure during the sperm’s month-long developmental window before pregnancy to di-2-ethylhexyl phthalate (DEHP), the most common phthalate. It is one of several endocrine-disrupting compounds used in plastics and personal care products. They say phthalate exposure in males has been associated with changes in semen quality, androgen levels and birth outcomes, but a mechanism for these effects has not been clearly identified.
Dr. Pilsner says that with this study, he would like to redefine reproductive health and how we regard environmental health. “For women wanting to get pregnant, we know they shouldn’t be smoking or drinking a lot, but no one has thought enough about the paternal side, about the father’s role. We will investigate whether dad’s environment can shape offspring growth and development. We hope this research opens up some insights into the role of dad during the two to three months before he and his partner try to become pregnant. In addition to his female partner, he may have some environmental responsibility prior to conception.”
Epigenetics refers to heritable change in gene expression without change in the DNA sequence, Dr. Mager explains. A relatively new field, epigenetics is useful in investigating the interaction of the environment with gene expression, which can change functions in an organism without changing its DNA sequence.
Dr. Pilsner adds, “With this mouse study, we will expose mouse sperm during a window that represents the time it takes for male germ cells to produce mature sperm.” This will complement Dr. Pilsner’s ongoing work from his human cohort study, “Sperm Environmental Epigenetics and Development Study” (SEEDS), which is examining the preconception paternal environmental influences on early-life development in collaboration with Baystate Medical Center’s IVF clinic in Springfield, Mass.
Dr. Mager explains that relatively little is known about how adult exposures to toxicants affect sperm epigenetics, and that “without such knowledge, advancing our understanding of paternal environmental determinants of reproductive health will be limited. Our long-term goal is to provide an epigenetic understanding of how paternal endocrine disrupting chemical exposure affects reproductive and offspring health, in both embryonic and placental tissue.”
He says that his and Dr. Pilsner’s dual research focus in environmental epigenetics and developmental epigenetics will use Dr. Mager’s established mouse model to study epigenetic dynamics during early development in embryos produced from parental strains of mice with different genetic backgrounds. The study will mate exposed and unexposed males to unexposed females with yet another genetic background. In this way, the researchers can trace epigenetic changes in offspring and whether such changes are the result of DEHP-exposed fathers.
This proposed research capitalizes on the Genetics, Genomics and Epigenetics group at UMass Amherst, the researchers say. They hope it will challenge the idea that sperm, once thought to only transmit genomic data, may be affected epigenetically by the environment and may have more direct effects on the next generation than previously thought.
Dr. Pilsner says, “Until now, no one has investigated the effect of environmental exposures on sperm epigenome in the context of the preconception period. Now we know there is this additional layer of information that can be inherited on top of genetic information via the sperm epigenome, which may influence the health and development of future generations.”