The phthalate DEHP undermines female fertility in mice

Prenatal exposure to DEHP increases male-to-female sex ratio in the F1 generation

Two studies in mice add to the evidence that the phthalate DEHP, a plasticizing agent used in auto upholstery, baby toys, building materials and many other consumer products, can undermine female reproductive health, in part by disrupting the growth and function of the ovaries.

Image of Jodi-Flaws
Comparative biosciences professor Jodi Flaws and her colleagues linked phthalate exposure during pregnancy to reproductive problems in mice parent and offspring, and to degradation of the function and structure of the ovaries.

2015 1st Study Abstract

This study tested the hypothesis that prenatal DEHP exposure affects female reproduction. To test this hypothesis, pregnant female CD-1 mice were orally dosed daily with tocopherol-stripped corn oil (vehicle control) or DEHP (20 μg/kg/day–750 mg/kg/day) from gestation day 11-birth. Pups were counted, weighed, and sexed at birth, ovaries were subjected to evaluations of follicle numbers on postnatal days (PNDs) 8 and 21, and fertility was evaluated at 3–9 months. The results indicate that prenatal DEHP exposure increased male-to-female ratio compared to controls. Prenatal DEHP exposure also increased preantral follicle numbers at PND 21 compared to controls. Further, 22.2% of the 20 μg/kg/day treated animals took longer than 5 days to get pregnant at 3 months and 28.6% of the 750 mg/kg/day treated animals lost some of their pups at 6 months. Thus, prenatal DEHP exposure alters F1 sex ratio, increases preantral follicle numbers, and causes some breeding abnormalities.

2015 2nd Study Abstract

Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis.

Sources and more information
  • The phthalate DEHP undermines female fertility in mice,, 16/04/2015.
  • Prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP) affects reproductive outcomes in female mice, sciencedirect pii/S0890623815000349, doi:10.1016/j.reprotox.2015.02.013, 9 March 2015.
  • Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles, sciencedirect pii/S0041008X15000617, doi:10.1016/j.taap.2015.02.010, 18 February 2015.

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