Paraben exposure alters cell cycle progression and survival of spontaneously immortalized secretory murine oviductal epithelial (MOE) cells

Abstract

The mammalian oviduct is a central organ for female reproduction as it is the site of fertilization and it actively transports the embryo to the uterus. The oviduct is responsive to ovarian steroids and thus, it is a potential target of endocrine disrupting chemicals. Parabens are antimicrobial compounds that are prevalently found in daily-used products. However, recent studies suggest that some parabens can impact female reproductive health. Yet, their effects on the oviduct are unknown. Here, we hypothesized that in vitro exposure of immortalized murine oviductal secretory epithelial (MOE) cells to methylparaben or propylparaben will result in disrupted cell cycle progression and increased cell death by dysregulation of molecular mechanisms that involve the cell cycle and apoptosis. Thus, we examined the effects of exposure to parabens on cell proliferation, cell cycle progression by flow cytometry, and mRNA levels of major cell cycle regulators and apoptotic factors, in MOE cells. Protein levels of estrogen and progesterone receptors were also quantified. Differences between treatments and controls were analyzed by linear mixed model followed by Dunnett post-hoc tests. The results indicate that methylparaben and propylparaben selectively reduce MOE cellular proliferation and colony numbers, compared to controls. Additionally, paraben exposure selectively dysregulates the progression through the cell cycle and decreases the levels of cell cycle regulators, compared to controls. Last, paraben selectively alters the levels of progesterone receptor. Overall, these findings suggest that parabens can affect mouse oviductal secretory epithelial cell proliferation and survival.

Keywords: Apoptosis; Cell cycle; Cosmetics; Estrogen; Oviduct; Paraben; Progesterone.