Effect of mono-(2-ethylhexyl) phthalate on steroid production of human granulosa cells

Reinsberg, Jochen; Wegener-Toper, Petra; Ven, Katrin van der; Ven, H. van der; Klingmueller, Dietrich

doi:10.1016/j.taap.2009.05.022

Cited by 74 publications

(47 citation statements)

References 35 publications

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“…The limitation of these previous studies is that they did not determine whether the effects on antral follicle size and estradiol production were direct effects on the follicle or were indirect effects caused by toxicity in other organ systems, namely the hypothalamus-pituitary axis. To combat this limitation, previous studies have shown that DEHP and MEHP decreased estradiol production and Cyp19a1 levels in murine and human granulosa cell cultures in vitro [53, 77-80]. However, the limitation of these studies is that they only utilized one somatic follicular cell type.…”

Section: Discussionmentioning

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

133

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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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Section: Discussionmentioning

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

133

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show abstract

“…Normal proliferation and function of granulosa cells possess great significance in female reproductive process, owing to its key role in deciding the fate of follicles (Matsuda et al, 2012). Emerging evidences have confirmed the adverse influences of MEHP on the viability and function of granulosa cells Reinsberg et al, 2009;Svechnikova et al, 2011), suggesting that granulosa cells may be target cells of MEHP in ovaries. Granulosa cells are a special kind of somatic cells in follicles.…”

Section: Discussionmentioning

confidence: 99%

The effect of mono-(2-ethylhexyl) phthalate on apoptosis of rat ovarian granulosa cells in vitro

Liu

Yuan

et al. 2015

Environmental Toxicology and Pharmacology

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“…In isolated mouse small preantral follicles, MEHP treatment (10-200 mM) resulted in increased inactivation of E 2 to estrone and a precocious increase in progesterone synthesis (Lenie & Smitz 2009). In human granulosa-lutein cells, MEHP (0.6-500 mmol/l) suppressed basal and FSH-, hCG-, and 8Br-cAMP-stimulated E 2 production, and decreased aromatase mRNA and activity (Reinsberg et al 2009). In porcine oocytecumulus complexes, DEHP increased progesterone production when given at 1 mM (Gunnarsson et al 2008).…”

Section: Plasticizers: Bisphenol a And Phthalatesmentioning

confidence: 95%

Endocrine-disrupting chemicals in ovarian function: effects on steroidogenesis, metabolism and nuclear receptor signaling

Craig¹,

Wang²,

Flaws³

2011

Reproduction

224

123

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Endocrine-disrupting chemicals (EDCs) are exogenous agents with the ability to interfere with processes regulated by endogenous hormones. One such process is female reproductive function. The major reproductive organ in the female is the ovary. Disruptions in ovarian processes by EDCs can lead to adverse outcomes such as anovulation, infertility, estrogen deficiency, and premature ovarian failure among others. This review summarizes the effects of EDCs on ovarian function by describing how they interfere with hormone signaling via two mechanisms: altering the availability of ovarian hormones, and altering binding and activity of the hormone at the receptor level. Among the chemicals covered are pesticides (e.g. dichlorodiphenyltrichloroethane and methoxychlor), plasticizers (e.g. bisphenol A and phthalates), dioxins, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons (e.g. benzo[a]pyrene).

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Effect of mono-(2-ethylhexyl) phthalate on steroid production of human granulosa cells

Cited by 74 publications

References 35 publications

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

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

The effect of mono-(2-ethylhexyl) phthalate on apoptosis of rat ovarian granulosa cells in vitro

Endocrine-disrupting chemicals in ovarian function: effects on steroidogenesis, metabolism and nuclear receptor signaling

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