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Prenatal exposure to phthalates damages reproductive tissue in female mice

BY Ananya Sen

Phthalates are a ubiquitous family of chemicals that are used every day. In a new study, researchers have investigated how these compounds affect tissue development in the reproductive systems of female mice offspring.

“Phthalates are found everywhere: building products, personal care products, food and beverage containers, and medical equipment,” said Jodi Flaws (EIRH co-leader/MME), a professor of comparative biosciences. “My research group focuses on how exposure to these environmental chemicals during pregnancy affect the offspring.”

Clockwise from top left: Jodi Flaws, Daryl Meling, and Justin Ka-Hong investigated the effects of phthalates on female mice offspring."
Clockwise from top left: Jodi Flaws, Daryl Meling, and Justin Ka-Hong investigated the effects of phthalates on female mice offspring.

Previous studies by the group have found that phthalate mixtures disrupt female reproduction, change organ weights, and cause ovarian cysts. In the current study, they are looking at how these mixtures affect ovarian steroidogenesis—a process that produces hormones that are required for reproduction—in female mice offspring. The researchers also looked at folliculogenesis, which is essential for fertility. Follicles are small fluid-filled sacs inside ovaries that contain the eggs. They undergo maturation before they release the egg during ovulation.

In the study, the pregnant mice were orally given either a control or a phthalate mixture every day from the first day of pregnancy till birth. “The reproductive system of the offspring develops during this window. The mice are no longer exposed to any phthalates after they are born,” Flaws said.

The ovaries of the female offspring were then collected 60 days after birth and the tissues and their hormone levels were analyzed. “We examined hormones such as estrogen, testosterone, and progesterone because they are important for normal fertility and tissue maintenance,” Flaws said.

The female mice whose mothers had been exposed to phthalates had lower levels of all three hormones compared to the controls. “Since the hormones are also important for other things in the body, such as cardiovascular health, bone health, and brain development, it is possible there are other effects of the mixture,” Flaws said.

“The main takeaway message is that if mothers are exposed to phthalates during their pregnancy, it can interfere with the female offspring’s ability to make normal levels of hormones,” Flaws said. “We saw that the mixture can inhibit the expression of important genes that are involved in making hormones.  

First author Sarah Gill, middle, with co-authors Kathleen DeLeon (left) and Emily Brehm (right).
First author Sarah Gill, middle, with co-authors Kathleen DeLeon on the left and Emily Brehm, right.

The researchers now collaborating with other researchers in the EIRH theme to see whether male offspring are similarly affected and to see whether phthalate exposure affects other female reproductive organs. They will also investigate whether these changes get passed on to subsequent generations. “We need to better understand the mechanism of these changes,” Flaws said. “We are interested in looking at whether these chemicals can increase tissue inflammation or whether they can affect other body parts such as the uterus, the hypothalamus, and the pituitary.”

Flaws is grateful to all the undergraduate researchers who performed the experiments: Sarah Gill, Kathleen Leon, and Justin Chiu. The other authors include Emily Brehm, a former graduate student, and Daryl Meling, a former postdoctoral fellow.

“Prenatal exposure to an environmentally relevant phthalate mixture alters ovarian steroidogenesis and folliculogenesis in the F1 generation of adult female mice” was published in Reproductive Toxicology. The work was funded by the National Institutes of Health and the Billie A. Field Fellowship.


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