Phthalates and bisphenol do not accumulate in human follicular fluid

Krotz, Stephan; Carson, Sandra Ann; Tomey, Cynthia; Buster, John E.

doi:10.1007/s10815-012-9775-1

Cited by 81 publications

(54 citation statements)

References 29 publications

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“…Furthermore, animals and plants accumulate DEHP in the body after contact . Several studies have shown that DEHP exposure is associated with testicular, mammary gland, liver, renal, and ovarian dysfunctions . These effects were found when exposure occurred at different times throughout the lifetime from the prenatal to the adult period, and may possibly involve different mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Identification of oxidative stress–related Xdh gene as a di(2‐ethylhexyl)phthalate (DEHP) target and the use of melatonin to alleviate the DEHP‐induced impairments in newborn mouse ovaries

Liu

Yan

et al. 2019

Journal of Pineal Research

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This study, using an in vitro ovary culture model, investigates the mechanisms through which di(2‐ethylhexyl)phthalate (DEHP) impairs germ cell cyst breakdown and primordial follicle assembly. The results indicate the latter effects exerted by 10 or 100 µmol/L DEHP in cultured newborn ovaries were associated with increased levels of reactive oxygen species (ROS) and apoptosis. Based on a transcriptome analysis, we found the expression of the oxidative stress–related gene Xdh (xanthine dehydrogenase) was significantly upregulated in DEHP‐cultured ovaries. Two treatments, namely Xdh RNAi or the addition of melatonin to the ovary culture, inhibited the increase in Xdh expression and ROS levels caused by DEHP and, at the same time, reduced apoptosis and the impairment of primordial follicle assembly in the treated ovaries. Together, the results identify Xdh gene as one of the major targets of DEHP in newborn ovaries and that the consequent increased level of ROS is possibly responsible for the increment of apoptosis and primordial follicle assembly impairment. At the same time, they highlight that melatonin alleviates the effects of DEHP as with other endocrine‐disrupting compounds on the ovary.

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Section: Introductionmentioning

confidence: 99%

Identification of oxidative stress–related Xdh gene as a di(2‐ethylhexyl)phthalate (DEHP) target and the use of melatonin to alleviate the DEHP‐induced impairments in newborn mouse ovaries

Liu

Yan

et al. 2019

Journal of Pineal Research

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show abstract

“…In fact, it is estimated that the range of daily human exposure to DEHP is between 3-30 μg/kg/day [3, 4]. Continuous, daily exposure to DEHP is a major concern because DEHP and its metabolite mono(2-ethylhexyl) phthalate (MEHP) have been identified in human blood samples [5, 6], urine samples [1, 5-9], amniotic fluid samples [10-12], cord blood samples from newborns [13, 14], breast milk samples [6], and in ovarian follicular fluid samples tested [15], indicating the ability of these chemicals to reach the ovary.…”

Section: Introductionmentioning

confidence: 99%

Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

Hannon¹,

Brannick²,

Wang³

et al. 2015

Toxicology and Applied Pharmacology

136

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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 (1-100μg/ml) for 24-96 hr to establish the temporal effects of DEHP on the follicle. Following 24-96 hr 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-hydorxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis.

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“…Specifically, the estimated range of daily human exposure to DEHP is 3-30 lg/kg/day [3,4]. Exposure to DEHP represents a public health concern because DEHP and its metabolite, mono(2-ethylhexyl) phthalate (MEHP), have been identified as top contaminants in human tissues such as blood [5,6], urine [1,[5][6][7][8][9], amniotic fluid [10][11][12], umbilical cord blood [13,14], breast milk [6], and ovarian follicular fluid [15]. Important from a toxicological standpoint, it is hypothesized that the toxicity of DEHP is mediated by the bioactive metabolite MEHP in many organ systems, including the ovary [16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

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

112

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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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Phthalates and bisphenol do not accumulate in human follicular fluid

Cited by 81 publications

References 29 publications

Identification of oxidative stress–related Xdh gene as a di(2‐ethylhexyl)phthalate (DEHP) target and the use of melatonin to alleviate the DEHP‐induced impairments in newborn mouse ovaries

Identification of oxidative stress–related Xdh gene as a di(2‐ethylhexyl)phthalate (DEHP) target and the use of melatonin to alleviate the DEHP‐induced impairments in newborn mouse ovaries

Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

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

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