Reproductive effects in F1 adult females exposed in utero to moderate to high doses of mono-2-ethylhexylphthalate (MEHP)

Moyer, Benjamin J.; Hixon, Mary L.

doi:10.1016/j.reprotox.2012.02.006

Cited by 80 publications

(57 citation statements)

References 36 publications

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“…Additionally, similar to previous phthalate work (28) vaginal openings in female BBP mice were significantly delayed compared to control mice (p=0.001; Figure 3b). …”

Section: Resultssupporting

confidence: 88%

“…Similar to the male mice, in the female mice we observed a decrease in estradiol as well as a delayed vaginal opening, which is an index associated with disrupted endocrine functioning (28). Associated with these alterations was a significant difference in distance and duration of exercise, but not speed in the BBP mice, confirming our hypothesis that exposure to BBP will alter physical activity.…”

Section: Discussionsupporting

confidence: 64%

“…This identification was performed daily by holding the mouse face up and examining the vaginal region with a spatula until the vaginal opening was visibly present. Previous studies (28) have suggested that in utero phthalate exposure delays vaginal openings in female offspring. As noted above, in males, anogenital distance [AD - distance from the anus to the base of the genitalia (22)] was measured weekly using a digital caliper (Mitutoyo Digimatic).…”

Section: Methodsmentioning

confidence: 95%

See 2 more Smart Citations

Environmental Endocrine Disruptor Affects Voluntary Physical Activity in Mice

Schmitt

Vellers

Porter

et al. 2016

Medicine &Amp; Science in Sports &Amp; Exercise

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INTRODUCTION Voluntary physical activity levels are regulated by sex hormones. The purpose of this study was to determine the effect of the endocrine disruptor benzyl butyl phthalate (BBP) on the regulation of physical activity in mice. METHODS Mouse dams were treated with 500 mg·kg−1·day−1 of BBP or vehicle on gestation days 9–16. Pups were weaned and analyzed for voluntary physical activity levels, puberty development, sex hormone levels, and body composition over a 20 week period. RESULTS Seventy-three offspring from BBP treated dams were studied (n=43 males, n=30 females). Endocrine disruption was indicated by decreased anogenital distances in BBP-treated male offspring at 10 (p=0.001) and 20 weeks (p=0.038) and delayed vaginal openings in BBP-treated female offspring (p=0.001). Further, there was a significant decrease in serum testosterone concentration in male mice between control and BBP at 10 weeks (p=0.039) and at 20 weeks (p=0.022). In female mice there was a significant increase in serum testosterone concentration in BBP mice at 20 weeks (p=0.002), and a significant increase in estrogen (estradiol) concentrations at 20 weeks in the control female mice (p=0.015). Overall, BBP mice ran significantly less distance (males, p=0.008; females, p=0.042) than controls. Other than a significant increase in BBP-treated males in fat mass at 20 weeks (p=0.040), there was no significant decrease in weight, lean mass, or fat mass in either female or male mice, regardless of treatment. CONCLUSION Maternal endocrine disruption altered hormone response, but not body composition in either sex of offspring, with a corresponding decreased activity throughout early adulthood in all offspring. These results suggest that exposure to common environmental endocrine disruptors in utero, can reduce and alter physical activity levels in offspring.

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“…Additionally, similar to previous phthalate work (28) vaginal openings in female BBP mice were significantly delayed compared to control mice (p=0.001; Figure 3b). …”

Section: Resultssupporting

confidence: 88%

Section: Discussionsupporting

confidence: 64%

Section: Methodsmentioning

confidence: 95%

See 1 more Smart Citation

Environmental Endocrine Disruptor Affects Voluntary Physical Activity in Mice

Schmitt

Vellers

Porter

et al. 2016

Medicine &Amp; Science in Sports &Amp; Exercise

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show abstract

“…Previous studies have shown that DEHP and MEHP accelerate primordial follicle recruitment in vivo [35,79,80]. The limitation of these studies is that they did not determine if these chemicals act directly on the ovary to elicit this response.…”

Section: Discussionmentioning

confidence: 96%

Mono(2-Ethylhexyl) Phthalate Accelerates Early Folliculogenesis and Inhibits Steroidogenesis in Cultured Mouse Whole Ovaries and Antral Follicles1

Hannon

Brannick

Wang

et al. 2015

Biology of Reproduction

109

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Humans are ubiquitously exposed to di(2-ethylhexyl) phthalate (DEHP), which is an environmental toxicant present in common consumer products. DEHP potentially targets the ovary through its metabolite mono(2-ethylhexyl) phthalate (MEHP). However, the direct effects of MEHP on ovarian folliculogenesis and steroidogenesis, two processes essential for reproductive and nonreproductive health, are unknown. The present study tested the hypotheses that MEHP directly accelerates early folliculogenesis via overactivation of phosphatidylinositol 3-kinase (PI3K) signaling, a pathway that regulates primordial follicle quiescence and activation, and inhibits the synthesis of steroid hormones by decreasing steroidogenic enzyme levels. Neonatal ovaries from CD-1 mice were cultured for 6 days with vehicle control, DEHP, or MEHP (0.2-20 lg/ml) to assess the direct effects on folliculogenesis and PI3K signaling. Further, antral follicles from adult CD-1 mice were cultured with vehicle control or MEHP (0.1-10 lg/ml) for 24-96 h to establish the temporal effects of MEHP on steroid hormones and steroidogenic enzymes. In the neonatal ovaries, MEHP, but not DEHP, decreased phosphatase and tensin homolog levels and increased phosphorylated protein kinase B levels, leading to a decrease in the percentage of germ cells and an increase in the percentage of primary follicles. In the antral follicles, MEHP decreased the mRNA levels of 17alpha-hydroxylase-17,20-desmolase, 17beta-hydroxysteroid dehydrogenase, and aromatase leading to a decrease in testosterone, estrone, and estradiol levels. Collectively, MEHP mediates the effect of DEHP on accelerated folliculogenesis via overactivating PI3K signaling and inhibits steroidogenesis by decreasing steroidogenic enzyme levels.

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“…However, the effects of prenatal phthalate exposure on female reproduction in the offspring are less extensively studied. Published studies have shown that gestational exposure to DEHP affects folliculogenesis [17], reduces oocyte quality [18], decreases steroidogenic capacity [18, 19], delays puberty [19], and decreases fertility [17, 18]. …”

Section: Introductionmentioning

confidence: 99%

Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice

Zhou

Gao

Flaws

2017

Toxicology and Applied Pharmacology

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Phthalates are used in a large variety of products, such as building materials, medical devices, and personal care products. Most previous studies on the toxicity of phthalates have focused on single phthalates, but it is also important to study the effects of phthalate mixtures because humans are exposed to phthalate mixtures. Thus, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects female reproduction in mice. To test this hypothesis, pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 μg/kg/day, 200 and 500 mg/kg/day) daily from gestational day 10 to birth. The mixture was based on the composition of phthalates detected in urine samples from pregnant women in Illinois. The mixture included 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. Female mice born to the exposed dams were subjected to tissue collections and fertility tests at different ages. Our results indicate that prenatal exposure to the phthalate mixture significantly increased uterine weight and decreased anogenital distance on postnatal days 8 and 60, induced cystic ovaries at 13 months, disrupted estrous cyclicity, reduced fertility-related indices, and caused some breeding complications at 3, 6, and 9 months of age. Collectively, our data suggest that prenatal exposure to an environmentally relevant phthalate mixture disrupts aspects of female reproduction in mice.

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Reproductive effects in F1 adult females exposed in utero to moderate to high doses of mono-2-ethylhexylphthalate (MEHP)

Cited by 80 publications

References 36 publications

Environmental Endocrine Disruptor Affects Voluntary Physical Activity in Mice

Environmental Endocrine Disruptor Affects Voluntary Physical Activity in Mice

Mono(2-Ethylhexyl) Phthalate Accelerates Early Folliculogenesis and Inhibits Steroidogenesis in Cultured Mouse Whole Ovaries and Antral Follicles1

Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice

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