People are exposed to a wide range of phthalates, a group of industrial chemicals, every day, via plastics, personal care products, and building materials. For pregnant women, the negative reproductive health consequences of such exposure pose a serious concern. Recent studies from the University of Illinois have found that prenatal exposure to Di-(2-ethylhexyl) phthalate (DEHP) can cause reproductive dysfunction and negatively impact male and female offspring in mice.

Xiyu Ge, a PhD candidate in molecular and integrative physiology, studies neurodevelopment and hypopituitarism as a member of professor Lori Raetzman’s lab in the Department of Molecular & Integrative Physiology. Ge and Raetzman are exploring the effects of prenatal exposure to phthalates specifically in the pituitary. Their work, “Prenatal exposure to the phthalate DEHP impacts reproduction-related gene expression in the pituitary” was recently published in Reproductive Toxicology. Research specialist Karen Weis and Jodi Flaws, a professor of comparative biosciences, also contributed to the research.

From left to right: PhD candidate Xiyu Ge and Dr. Lori Raetzman.

“Even though we know that DEHP metabolizes in our body very fast, there could be long-term effects and even transgenerational effects,” Ge explains. The federal government regulates the amount of DEHP in water and products like water bottles, however, more studies are needed, they say. “Maybe your mom, your grandma, whatever last past generation was exposed [to DEHP], some of those effects could be inherited or translated epigenetically to the descendent or to the offspring. So it’s important, and researchers have already found there are definitely transgenerational effects in both male and female [mice].”

Current research has focused mostly on phthalates’ effect on gonads, but the Raetzman lab is interested in the pituitary gland. Its role in the reproductive system is often overlooked or underestimated, she said. Ge and Raetzman’s research has revealed the pituitary gland to be a critical part of phthalates’ damage pathway. The pituitary could be a potential target in efforts to mitigate exposure of phthalates. Additionally, their work raises questions about what is a safe level of exposure to DEHP.

“Part of what we should be doing as scientists is advocating for more research or reassessment of that authorized level,” Raetzman says. “I think that’s also what our research contributes to in terms of the common good because the way [federal agencies] determine the safe level of these chemicals is to assay things like liver weight or cancer, but they rarely look at other important endpoints like reproduction.”

One of the first steps to mitigation is understanding the underlying mechanisms of the phthalate’s damage to the reproductive system. The pituitary gland regulates reproductive glands and secretes hormones that are necessary for reproduction, however, existing research on phthalates tends to overlook the pituitary’s role in reproduction. Raetzman and Ge focused on the effects of DEHP in the pituitary gland. They were particularly interested in critical periods of development, in which the offspring may be more vulnerable to DEHP. For their studies, the researchers used mice models.

In their experiments, Raetzman and Ge utilized concentrations of DEHP that were very similar, and in some cases lower, than the normal range of human exposure to DEHP. They discovered that phthalates can have anti-androgenic effects at these concentrations in mice. Additionally, through animal and culture experiments they were able to deduce DEHP’s direct effect on the pituitary gland via activation of aryl hydrocarbon receptor signaling and alteration of gonadotropin expression.

“We are constantly exposed to phthalates, so it will be hard to get rid of entirely,” Raetzman acknowledges. “But we want to find ways to mitigate it.”

Ge says although the negative impacts on the reproductive system may not be immediately apparent, that doesn’t make their findings any less urgent when it comes to possible implications for human infertility in future generations.

“What we want to do is bring awareness and let people know that you can intervene early enough if you have the awareness to do so,” she says.