Di (2-ethylhexyl) phthalate exposure impairs meiotic progression and DNA damage repair in fetal mouse oocytes in vitro

Liu, Jing-Cai; Lai, Fang-Nong; Li, Ling; Sun, Xiao‐Feng; Cheng, Shun‐Feng; Ge, Wei; Wang, Yufeng; Li, Lan; Zhang, Xifeng; Felici, Massimo De; Dyce, Paul W.; Shen, Wei

doi:10.1038/cddis.2017.350

Cited by 72 publications

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“…DEHP, an environmental contaminant, is extensively used in various applications and almost found everywhere in the environment . More and more studies indicate that DEHP does harm to mammalian reproductive system . Particularly, DEHP exposure is associated with the changes in female ovarian function, as well as increased risk of endometriosis, preterm delivery, and various pregnancy complications .…”

Section: Discussionmentioning

confidence: 99%

“…Researches have reported that DEHP exposure on human ranges from 3 to 30 μg/kg/d . To simulate the concentration in vivo, the experimental concentration of DEHP was selected to be 10 or 100 μmol/L according to the previous experiments in vitro . Equal concentrations of solvents were added to the culture medium as the control group.…”

Section: Methodsmentioning

confidence: 99%

“…Paraffin sections were firstly incubated at 60°C for 2 hours, followed by a rehydrated procedure before deparaffinization. Then, primary antibody was added as described above . After adding FITC‐conjugated goat anti‐rabbit secondary antibody (Beyotime, A0562), the sections were incubated with proteinase K for 14 minutes.…”

Section: Methodsmentioning

confidence: 99%

“…DEHP affects several processes during ovary development with the changes being observed mainly in cellular and animal models. For example, in an in vitro study with mouse embryonic ovaries, DEHP altered the first meiotic division of the oocytes by impairing their capability to repair DNA double‐strand breaks induced by meiotic recombination . Moreover, maternal DEHP exposure altered DNA methylation of fetal oocyte imprinted genes, with deleterious consequence for offspring oogenesis .…”

Section: Introductionmentioning

confidence: 99%

“…For example, in an in vitro study with mouse embryonic ovaries, DEHP altered the first meiotic division of the oocytes by impairing their capability to repair DNA double-strand breaks induced by meiotic recombination. 13 Moreover, maternal DEHP exposure altered DNA methylation of fetal oocyte imprinted genes, with deleterious consequence for offspring oogenesis. 14 In neonatal ovaries, DEHP exposure increased oocyte apoptosis associated with reduced expression of germ cell-specific genes, 15 depressed autophagy by activating AMPK-SKP2-CARM1 signaling, 16 and impaired oocyte cyst breakdown and primordial follicle assembly by disrupting the estrogen receptor (ER) and Notch signaling.…”

mentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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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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Guardians of Oocyte Quality

Ruebel

Latham

2018

Encyclopedia of Life Sciences

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Oocyte quality is fundamental to assisted reproduction, agricultural livestock productivity and species preservation. Mammalian oocytes develop in close coordination with somatic follicle cells of the ovary, and manifest remarkable molecular mechanisms that serve as guardians of oocyte quality and integrity. Genome and mitochondrial integrity are major aspects of oocyte quality determination. Ongoing research is revealing the details of these mechanisms, and how they help protect oocytes from detrimental effects of exogenous factors. Key Concepts Oocyte quality is essential for assisted reproduction success. Development of the oocyte involves an intricate set of bidirectional signals between the oocyte, cumulus cells and follicular fluid components, which can impact the quality of the oocyte. Chromosome segregation and adaptability to DNA damage are critical for the integrity of oocyte's genome. Energy production, proper distribution of mitochondria and regulation of fusion/fission are essential for maintaining the integrity of the mitochondria and oocyte developmental competence. Overall, oocyte maturation and development is a highly regulated process, and disruption in this process could comprise the mitochondrial and genomic integrity, further impacting the health of the oocytes. There are a variety of extrinsic factors, such as maternal health, maternal diet and environmental exposures, that can further impact oocyte quality. Therapies such as antioxidant, melatonin, CoQ10 and resveratrol treatments have been suggested to improve oocyte quality, but more studies are needed to determine efficacy. Novel biomarkers of oocyte quality need to be discovered.

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Revealing the effects of maternal di(2‐ethylhexyl) phthalate exposure on the progression of early meiosis in female foetal germ cells at single‐cell resolution

Yan

Wang

et al. 2022

Clinical & Translational Med

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Dear EditorTo provide in-depth insight into how di(2-ethylhexyl) phthalate (DEHP) influences early oogenesis, this study outlined the effects of maternal DEHP exposure on the meiotic progression of female germ cells in mice foetuses in vivo. DEHP is widely distributed in our lives owing to the daily use of polyvinyl chloride in plastic products. 1,2 Multiple reports have demonstrated that DEHP intake is particularly harmful to pregnant women as there is strong evidence that DEHP can pass through the maternal-foetal barrier. 3,4 However, the exact effect of DEHP on meiotic initiation of foetal germ cells, a critical biological event for successful oogenesis during pregnancy, is not fully understood. 5 In this research, we performed single-cell RNA sequencing (scRNA-seq) to analyse the foetal ovaries at 12.5 days post coitum (dpc) and 14.5 dpc after maternal DEHP exposure.Normal saline or 40 μg/kg body weight DEHP were orally administrated to pregnant mice daily from 6.5 dpc, and 12.5 dpc or 14.5 dpc foetal ovaries were isolated for scRNA-seq (Figure 1A). A total of 25 270 high-quality cells were selected for further analysis (Figure S1A,B). After dimensionality reduction using uniform manifold approximation and projection (UMAP), these cells were divided into 18 clusters and seven types of cells were identified according to their canonical marker expression, including germ cells, granulosa cells, mesothelial cells, interstitial cells, endothelial cells, erythroid cells, and immune cells (Figure 1B-D; Figure S1C). 6 To provide a fine-scale analysis of how maternal DEHP exposure affects the meiotic transcriptome, germ cell clusters were extracted for further analysis (Figure 2A-D). After UMAP analysis, germ cells were subdivided into 16 transcriptionally distinct clusters whose expression patterns, from left to right in the UMAP plot, correspond to pre-meiosis, pre-leptotene, leptotene, zygoteneThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Di (2-ethylhexyl) phthalate exposure impairs meiotic progression and DNA damage repair in fetal mouse oocytes in vitro

Cited by 72 publications

References 42 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

Guardians of Oocyte Quality

Revealing the effects of maternal di(2‐ethylhexyl) phthalate exposure on the progression of early meiosis in female foetal germ cells at single‐cell resolution

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