Water disinfection byproduct disrupts reproductive hormones, damages pituitary in female mice

A byproduct formed during water disinfection disrupts hormones that regulate reproduction in female mice, found professor Lori Raetzman (left) and PhD student Rachel Gonzalez. Photo by L. Brian Stauffer

Chemical disinfection makes water from both natural sources and wastewater streams drinkable; however, the process also creates byproducts, not all of which are understood or regulated. A new study from University of Illinois Urbana-Champaign researchers has found that one byproduct disrupts hormones in the brain that regulate the female reproductive cycle in mice and also damages cells in the pituitary gland.

Iodoacetic acid, or IAA, is created when an oxidizing disinfectant such as chlorine reacts with the iodide naturally present in water, said study leader Lori Raetzman, a professor of molecular and integrative physiology. The new study’s findings of IAA’s effects on reproductive regulation in the brain complement previous work by study co-author Jodi Flaws, a professor of comparative biosciences, which found that IAA also disrupts function in and causes damage to ovary cells, indicating that the chemical could impact the entire reproductive system.

“We know we need to disinfect water, but the water that’s coming out of our taps isn’t pure – regulators only screen for the things they know about. Water regulatory bodies have not been looking for IAA,” Raetzman said. “This study is contributing to the growing body of evidence that suggests that IAA may impact reproduction, so it might be reasonable to have screening for this too, and to establish a safe level for it.”

In the new study, published in the journal Toxicological Sciences, the researchers gave mice drinking water containing IAA at levels comparable to possible human exposure, as well as a control group of mice that were given water with no IAA present, for 35-40 days. Then they measured the production of reproduction-regulating factors in two key parts of the neuroendocrine system – the hypothalamus and the pituitary.

“Mice are often used as models for the human reproductive system because they have estrous cycles that are similar to human menstrual cycles,” said graduate student Rachel Gonzalez, the first author of the study. “The hypothalamus and the pituitary are the master regulators of the endocrine system. It’s a good foundation to say that a human exposed to a certain amount of IAA could potentially have similar effects.”

The researchers found that, even at low levels, IAA disrupted production of a key reproduction-regulating factor in the hypothalamus. At higher levels, IAA reduced pituitary production of follicle-stimulating hormone, a key hormone for promoting egg maturation in the ovaries leading up to ovulation. The hormone also is linked to estrogen production.

“Hypothetically, a persistent reduction in follicle-stimulating hormone over a long term could potentially lead to an issue with the development of follicles in the ovaries, which house the eggs and release them during ovulation,” Gonzalez said. “In their study of ovarian effects, our colleague in the Flaws lab did see issues with folliculogenesis in cell cultures, so this work shows that IAA may be affecting the whole reproductive axis.”

In addition, the researchers saw toxic effects, including DNA damage, in the pituitaries of the mice that consumed IAA. Because of this finding and the earlier findings from the Flaws lab regarding ovarian cell damage, the researchers are now investigating whether and how exposing pregnant mice to IAA in drinking water affects their pups.

“These chemicals will cause breaks in the DNA that, if not repaired properly, could lead to mutations in the DNA that would be propagated and might lead to further dysfunction – either dysfunction of the tissue because the cells aren't working properly or diseases like cancer,” Raetzman said. “Some of the importance of this is because DNA damage could be transmitted generationally, so if mom’s eggs get damaged, they may pass on DNA damage to the offspring.”

The researchers hope that the continued study of IAA’s effects on both the neuroendocrine and ovarian aspects of the female reproductive system can help establish a safe level of exposure to guide future regulations, Raetzman said.

The National Institutes of Health supported this work.

Written by Liz Ahlberg Touchstone, University of Illinois News Bureau

Read the full research paper.

November 24, 2021 All News