Urinary concentrations of phthalate metabolites in early pregnancy associated with clinical pregnancy loss in Chinese women

Gao, Hui; Zhang, Yunwei; Huang, Kun; Yan, Shuangqin; Mao, Leijing; Ge, Xing; Xu, Yu; Xu, Yuanyuan; Sheng, Jie; Zhang, Jin; Zhu, Peng; Tao, X Y; Hao, Jiahu; Tao, Fangbiao

doi:10.1038/s41598-017-06450-2

Cited by 40 publications

(18 citation statements)

References 60 publications

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“…Bottlenose dolphin exposure to DEHP and DEP is concerning due to laboratory and human studies linking these chemicals to adverse health effects including altered hormone synthesis and transport (ATSDR, ; Meeker & Ferguson, ; Sathyanarayana et al, ], male genital developmental abnormalities (ATSDR, ; Swan, ), reproductive impairment (e.g., lower birth weight, Messerlian et al, ; preterm birth, Meeker et al, ; delayed time to pregnancy, Thomsen et al, ; pregnancy loss, H. Gao et al, ), and liver toxicoses including liver cancer (ATSDR, ). In fact, MEHP concentrations measured in the dolphins in this study (GM = 1.9 ng/ml; Range = 0.9–5.9 ng/ml) were at comparable levels reported to be associated with a reduced probability of reproductive success in humans (Hauser et al, ).…”

Section: Discussionmentioning

confidence: 99%

Urinary Phthalate Metabolites in Common Bottlenose Dolphins (Tursiops truncatus) From Sarasota Bay, FL, USA

et al. 2018

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Phthalates are chemical additives to common consumer goods including cleaning products, cosmetics, personal care products, and plastic. Because they are not chemically bound to these products and are widely used, the potential for environmental contamination is significant. Phthalates and their metabolites have been associated with endocrine disruption and reproductive impairment, among other adverse health effects, in laboratory animals and human epidemiologic studies. Common bottlenose dolphins (Tursiops truncatus) are vulnerable to environmental pollutants due to their apex position in the food chain, long life spans, and habitat overlap with developed coastal areas. The objective of this study was to quantify phthalate metabolite concentrations in urine collected from bottlenose dolphins in Sarasota Bay, Florida, during May 2016 (n = 7) and May 2017 (n = 10). Screening of nine phthalate monoester metabolites in bottlenose dolphin urine was performed by liquid chromatography tandem mass spectrometry using methods adapted from those used for analyzing human samples. At least one phthalate metabolite was detected in 71% of the dolphins sampled across both years, with the highest concentrations detected for monoethyl phthalate (MEP; GM = 5.4 ng/ml; 95%CI: 1.3–22.0 ng/ml) and mono‐(2‐ethylhexyl) phthalate (MEHP; GM = 1.9 ng/ml; 95%CI: 1.1–3.2 ng/ml). These data demonstrate exposure to two of the most commonly used phthalates in commercial manufacturing, diethyl phthalate (DEP) and di‐2‐ethylhexyl phthalate (DEHP). This study establishes methods for urinary detection of phthalate metabolites in marine mammals and provides baseline data to address a significant and growing, yet poorly understood, health threat to marine wildlife.

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Section: Discussionmentioning

confidence: 99%

Urinary Phthalate Metabolites in Common Bottlenose Dolphins (Tursiops truncatus) From Sarasota Bay, FL, USA

et al. 2018

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“…A Danish prospective cohort study ( n = 128) reported that maternal urinary MEHP concentrations measured on the 10th day of the last menstrual period before conception were positively associated with subclinical embryonic loss (<6 weeks' gestation), but inversely associated with clinical pregnancy loss (>6 weeks of gestation) ( 59 ). However, in a large population study ( n = 3,220), maternal urinary concentrations of MEP, MEOHP, MEHHP, and ΣHMWP were significantly correlated to higher odds of embryonic loss (during 6–10 weeks' gestation), and MEHHP was positively associated with fetal loss (during 11–27 gestational weeks) after stratified analysis by gestational weeks ( 60 ). With respect to subfertile couples conceiving through medically assisted reproduction, urinary concentrations of DEHP metabolites (MEHP, MEHHP, MEOHP, and the molar sum of DEHP metabolites) during fertility treatment cycle were positively associated with both subclinical embryonic loss and pregnancy loss before 20 gestational weeks ( 63 ).…”

Section: Prenatal Phthalate Exposure and Pregnancy Lossmentioning

confidence: 93%

“…Phthalate exposure may affect pregnancy maintenance and cause pregnancy loss because of the endocrine disruption. Most epidemiologic evidence showed phthalate exposure was related to higher odds of pregnancy loss not only in couples conceiving naturally (59)(60)(61)(62) but also among women undergoing medically assisted reproduction (63) ( Table 3).…”

Section: Prenatal Phthalate Exposure and Pregnancy Lossmentioning

confidence: 99%

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The Endocrine Disruption of Prenatal Phthalate Exposure in Mother and Offspring

Qian

Shao

Ying

et al. 2020

Front. Public Health

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Phthalates are a group of ubiquitous synthetic endocrine-disrupting chemicals. Fetal and neonatal periods are particularly susceptible to endocrine disorders, which prenatal exposure to phthalates causes. There is increasing evidence concerning the potential endocrine disrupting for phthalate exposure during pregnancy. This article aims to review the endocrine impairment and potential outcomes of prenatal phthalate exposure. Prenatal exposure phthalates would disrupt the levels of thyroid, sex hormone, and 25-hydroxyvitamin D in pregnant women or offspring, which results in preterm birth, preeclampsia, maternal glucose disorders, infant cryptorchidism, infant hypospadias, and shorter anogenital distance in newborns, as well as growth restriction not only in infants but also in early adolescence and childhood. The relationship of prenatal phthalate exposure with maternal and neonatal outcomes in human beings was often sex-specific associations. Because of the potentially harmful influence of prenatal phthalate exposure, steps should be taken to prevent or reduce phthalate exposure during pregnancy.

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“…2018), preterm birth (Ferguson et al. 2014), pregnancy loss (Gao et al. 2017b), and altered neurodevelopment in infants (Engel et al.…”

Section: Introductionmentioning

confidence: 99%

The Role of Peroxisome Proliferator–Activated Receptor Gamma (PPARγ) in Mono(2-ethylhexyl) Phthalate (MEHP)-Mediated Cytotrophoblast Differentiation

Shoaito

Petit

Chissey

et al. 2019

Environ Health Perspect

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Background:Phthalates are environmental contaminants commonly used as plasticizers in polyvinyl chloride (PVC) products. Recently, exposure to phthalates has been associated with preterm birth, low birth weight, and pregnancy loss. There is limited information about the possible mechanisms linking maternal phthalate exposure and placental development, but one such mechanism may be mediated by peroxisome proliferator–activated receptor γ (PPARγ). PPARγ belongs to the nuclear receptor superfamily that regulates, in a ligand-dependent manner, the transcription of target genes. Studies of PPARγ-deficient mice have demonstrated its essential role in lipid metabolism and placental development. In the human placenta, PPARγ is expressed in the villous cytotrophoblast (VCT) and is activated during its differentiation into syncytiotrophoblast.Objectives:The goal of this study was to investigate the action of mono(2-ethylhexyl) phthalate (MEHP) on PPARγ activity during in vitro differentiation of VCTs.Methods:We combined immunofluorescence, PPARγ activity/hCG assays, western blotting, and lipidomics analyses to characterize the impacts of physiologically relevant concentrations of MEHP (0.1, 1, and 10μM) on cultured VCTs isolated from human term placentas.Results:Doses of 0.1μM and 1μM MEHP showed significantly lower PPARγ activity and less VCT differentiation in comparison with controls, whereas, surprisingly, a 10μM dose had the opposite effect. MEHP exposure inhibited hCG production and significantly altered lipid composition. In addition, MEHP had significant effects on the mitogen-activated protein kinase (MAPK) pathway.Conclusions:This study suggests that MEHP has a U-shaped dose–response effect on trophoblast differentiation that is mediated by the PPARγ pathway and acts as an endocrine disruptor in the human placenta. https://doi.org/10.1289/EHP3730

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Urinary concentrations of phthalate metabolites in early pregnancy associated with clinical pregnancy loss in Chinese women

Cited by 40 publications

References 60 publications

Urinary Phthalate Metabolites in Common Bottlenose Dolphins (Tursiops truncatus) From Sarasota Bay, FL, USA

Urinary Phthalate Metabolites in Common Bottlenose Dolphins (Tursiops truncatus) From Sarasota Bay, FL, USA

The Endocrine Disruption of Prenatal Phthalate Exposure in Mother and Offspring

The Role of Peroxisome Proliferator–Activated Receptor Gamma (PPARγ) in Mono(2-ethylhexyl) Phthalate (MEHP)-Mediated Cytotrophoblast Differentiation

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