Propylparaben may alter mammary gland, reduce breast cancer protection in pregnancy
Exposure to propylparaben, an endocrine-disrupting chemical used as a preservative in personal care products and food, may alter normal pregnancy-related breast changes, according to data presented at the ENDO annual meeting.
Low levels of propylparaben exposure were associated with disruptions to pregnancy-induced mammary gland changes in pregnant and lactating mice, according to researchers, who said they believe similar effects could be found in women.
“Though the design of this study is limited to effects in mice, propylparaben exposures, at levels deemed safe for humans, disrupted normal mammary gland changes associated with reduced breast cancer risk,” Joshua P. Mogus, MS, a PhD student in the department of environmental health sciences at the University of Massachusetts Amherst School of Public Health and Health Sciences, told Healio.
Mogus and colleagues analyzed the effects of propylparaben exposure in a group of pregnant mice aged 6 to 8 weeks. Doses of propylparaben were administered throughout pregnancy and lactation, for a period of 40 days, to three treatment groups. The first group was given a 20 g/kg dose of propylparaben daily, the second 100 g/kg of propylparaben daily, and the third a 10,000 g/kg dose of propylparaben per day. The lowest dose of propylparaben is equivalent to about the intake of the 95th percentile of pregnant women in the U.S., and the highest dose is similar to the toxicologic no-observed adverse effect level for propylparaben. Researchers also included a pregnant control cohort exposed to tocopherol-stripped corn oil vehicle, and a nonpregnant control group administered corn oil on the same dosing regimen as the parous control group.
“Women are exposed to propylparaben through the regular use of consumer products, but it would be unethical to purposefully dose them with an environmental chemical if we suspected it could negatively impact their health,” study co-author Laura Vandenberg, PhD, associate professor of environmental health sciences at University of Massachusetts Amherst, told Healio. “This is one very important reason why we rely on animal models to study chemicals. The other reason we need data from rodents is that we can maintain a group of unexposed animals that we use as a comparison group. In humans, it would be quite difficult to maintain a group of unexposed women because propylparaben — and other similar chemicals — are so widely used.”
After 40 days of propylparaben exposure, the mice were untreated for 5 weeks to allow the completion of mammary gland involution, the natural regression of the organ following weaning. After the 5 weeks ended, the mice were euthanized and the mammary glands dissected and analyzed for histomorphology changes, hormone receptor expression, number of immune cells and gene expression.
Propylparaben associated with mammary gland changes
Mice exposed to 20 g/kg and 100 g/kg propylparaben doses had an increase in Ki67-positive cells, a marker of cell proliferation, compared with the pregnant control group, although propylparaben did not have an effect on the number of stem cells. Furthermore, mammary glands from mice exposed to all three doses of propylparaben had alterations in the number of mammary structures, which were significantly less-dense than in the pregnant control group.
Several immune cell types were also altered in the propylparaben exposure groups. CD3+ cells were significantly higher in pregnant controls compared with nonpregnant controls. Mice in the 20 g/kg group had significantly more CD3+ cells compared with all other groups.
In the identification and analysis of M2 macrophages, the 100 g/kg dose group had intermediate levels of CD163+/F480+ cells significantly different from both control groups. No significant difference was found in the number of CD206+/F480+ cells compared with both control cohorts.
Implications for pregnant women
Although the findings were observed in mice and not humans, Vandenberg noted the mice were exposed to propylparaben levels equivalent to what women are commonly exposed to in the U.S.
“Our data suggest that even these low-level exposures alter health outcomes in mice,” Vandenberg said. “Of course, there are important differences in physiology between humans and mice, so we cannot say for certain if these same effects would be observed in human populations. Yet, we use rodents to screen pharmaceuticals, chemicals and other environmental agents, so these results should not be dismissed.”
Mogus said some of the mammary gland changes observed in the mice could erase some of the protections pregnant women have to reduce their risk for breast cancer, making it important to analyze whether propylparaben influences the risk for breast cancer in future studies. In the meantime, public health officials should advocate for the reduction of propylparaben and pregnant women should take steps to reduce their exposure.
“Women are exposed to propylparaben in many everyday items, such as cosmetics or even packaged foods,” Mogus said. “Pregnant women may want to consider consulting with their physicians on how to limit contact with these propylparaben products.”
Reference:
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Mogus JP, et al. Exposure to the endocrine disruptor, propylparaben, during pregnancy and lactation, alters typical parity-induced reorganization of the mouse mammary gland. Presented at: ENDO annual meeting; March 20-23, 2021 (virtual meeting).