Exposure to propylparaben interferes with parity of the mouse mammary gland and induces long-term alterations to mammary gland structure, according to the results of a mouse-model study published in Endocrinology.

Despite continued concerns over the safety of parabens, few studies have actually evaluated the outcomes of propylparaben exposure in animal models. To rectify this, researchers studied the long-term effects of propylparaben exposures during pregnancy and lactation in a mouse model.

Six- to 8-week-old mice were used for this study. Mice divided into 4 groups; the first 3 groups were exposed to 1 of 3 doses of propylparaben (20, 100, or 10,000 µg/kg/day [20PP, 100PP, and 10,000PP]). The mice mated, gave birth, and nursed. They were then euthanized, and the third pectoral pair of mammary glands were dissected from the skin. The glands were processed through a series of alcohols and xylene and then preserved. Standard methods and commercial antibodies were used for immunochemistry targeting estrogen receptor alpha (ERa), progesterone receptor (PR), Ki67, Wnt5a, B cells, CD8a cells, FoxP3 expressing cells, and CD3 positive cells. Immunofluorescence co-staining of CD163/F480 positive cells and mannose receptor CD206/F480 positive cells.


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Investigators evaluated female mice from all 4 groups for both differences in pregnancy outcomes and pup survivability. Gestation length was increased by roughly 12 hours in all 3 groups treated with propylparaben, although the increase was not statistically significant. No statistically significant effects on litter size in these groups were noted.

Evaluation of the whole-mounted mammary glands—collected 5 weeks after weaning from the treated and age-matched nulliparous control mice—was conducted to determine if and how propylparaben exposure during pregnancy and lactation alters morphology.

Per the researchers, the volume fraction of the gland, comprised of ductal epithelium, was increased in parous controls compared with nulliparous control female mice. Volume fraction of ductal epithelium was also significantly decreased compared with control mice, but significantly higher than in the nulliparous controls—consistent with an intermediate phenotype.

Propylparaben exposure was found not only to reduce the effects of parity, but also to increase the proliferation of ERα-mediated genes, in addition to the induction of “modest alterations to expression.” Propylparaben also altered parity of the mice related to several immune cell types found in the mammary gland.

“In several of these outcomes, propylparaben reduced the effect of parity, creating intermediate phenotypes,” the researchers wrote. “Taken together, our study indicates that propylparaben exposure during pregnancy and lactation alters the remodeling of the mammary gland that normally occurs during lactation and involution.”

“Our study provides strong evidence that propylparaben disrupts the endocrine system by altering mRNA expression of hormone pathways, immune cell populations, rates of epithelial cell proliferation, and hormone responsive morphology,” they concluded. “Our results indicate that propylparaben exposure during pregnancy and lactation alters mammary gland development, potentially diminishing the protective effects of parity.”

“Importantly,” they added, “many of these effects were observed at doses that are relevant to exposure in pregnant American women.”

Future studies, the researchers noted, with larger sample sizes are needed to further investigate these effects and outcomes.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Mogus JP, LaPlante CD, Bansal R, et al. Exposure to propylparaben during pregnancy and lactation induces long-term alterations to the mammary gland in mice. Published online March 16, 2021. Endocrinology. doi: 10.1210/endocr/bqab041