PDF(Pubmed)
Abstract：
UNASSIGNED: Exposure to obesogenic chemicals has been reported to result in enhanced adipogenesis, higher adipose tissue accumulation, and reduced ovarian hormonal synthesis and follicular function. We have reported that organotins [tributyltin (TBT) and triphenyltin (TPT)] dysregulate cholesterol trafficking in ovarian theca cells, but, whether organotins also exert lipogenic effects on ovarian cells remains unexplored.
UNASSIGNED: We investigated if environmentally relevant exposures to organotins [TBT, TPT, or dibutyltin (DBT)] induce lipid dysregulation in ovarian theca cells and the role of the liver X receptor (LXR) in this effect. We also tested the effect of TBT on oocyte maturation and neutral lipid accumulation, and lipid-related transcript expression in cumulus cells and preimplantation embryos.
UNASSIGNED: Primary theca cell cultures derived from human and ovine ovaries were exposed to TBT, TPT, or DBT (1, 10, or 50 ng/ml). The effect of these chemical exposures on neutral lipid accumulation, lipid abundance and composition, lipid homeostasis-related gene expression, and cytokine secretion was evaluated using liquid chromatography-mass spectrometry (LC-MS), inhibitor-based methods, cytokine secretion, and lipid ontology analyses. We also exposed murine cumulus-oocyte complexes to TBT and evaluated oocyte maturation, embryo development, and lipid homeostasis-related mRNA expression in cumulus cells and blastocysts.
UNASSIGNED: Exposure to TBT resulted in higher intracellular neutral lipids in human and ovine primary theca cells. In ovine theca cells, this effect was dose-dependent, independent of cell stage, and partially mediated by LXR. DBT and TPT resulted in higher intracellular neutral lipids but to a lesser extent in comparison with TBT. More than 140 lipids and 9 cytokines were dysregulated in TBT-exposed human theca cells. Expression of genes involved in lipogenesis and fatty acid synthesis were higher in theca cells, as well as in cumulus cells and blastocysts exposed to TBT. However, TBT did not impact the rates of oocyte maturation or blastocyst development.
UNASSIGNED: TBT induced dyslipidemia in primary human and ovine theca cells, which may be responsible for some of the TBT-induced fertility dysregulations reported in rodent models of TBT exposure. https://doi.org/10.1289/EHP13955.
UNASSIGNED: We investigated if environmentally relevant exposures to organotins [TBT, TPT, or dibutyltin (DBT)] induce lipid dysregulation in ovarian theca cells and the role of the liver X receptor (LXR) in this effect. We also tested the effect of TBT on oocyte maturation and neutral lipid accumulation, and lipid-related transcript expression in cumulus cells and preimplantation embryos.
UNASSIGNED: Primary theca cell cultures derived from human and ovine ovaries were exposed to TBT, TPT, or DBT (1, 10, or 50 ng/ml). The effect of these chemical exposures on neutral lipid accumulation, lipid abundance and composition, lipid homeostasis-related gene expression, and cytokine secretion was evaluated using liquid chromatography-mass spectrometry (LC-MS), inhibitor-based methods, cytokine secretion, and lipid ontology analyses. We also exposed murine cumulus-oocyte complexes to TBT and evaluated oocyte maturation, embryo development, and lipid homeostasis-related mRNA expression in cumulus cells and blastocysts.
UNASSIGNED: Exposure to TBT resulted in higher intracellular neutral lipids in human and ovine primary theca cells. In ovine theca cells, this effect was dose-dependent, independent of cell stage, and partially mediated by LXR. DBT and TPT resulted in higher intracellular neutral lipids but to a lesser extent in comparison with TBT. More than 140 lipids and 9 cytokines were dysregulated in TBT-exposed human theca cells. Expression of genes involved in lipogenesis and fatty acid synthesis were higher in theca cells, as well as in cumulus cells and blastocysts exposed to TBT. However, TBT did not impact the rates of oocyte maturation or blastocyst development.
UNASSIGNED: TBT induced dyslipidemia in primary human and ovine theca cells, which may be responsible for some of the TBT-induced fertility dysregulations reported in rodent models of TBT exposure. https://doi.org/10.1289/EHP13955.
摘要：
■据报道，暴露于生性化学物质会导致脂肪生成增强，较高的脂肪组织积累，减少卵巢激素合成和卵泡功能。我们已经报道了有机锡[三丁基锡（TBT）和三苯基锡（TPT）]失调卵巢卵泡膜细胞中的胆固醇运输，但是,有机锡是否也对卵巢细胞发挥脂肪生成作用尚待研究.
■我们调查了有机锡[TBT，TPT,或二丁基锡（DBT）]诱导卵巢卵泡膜细胞中的脂质失调以及肝X受体（LXR）在这种作用中的作用。我们还测试了TBT对卵母细胞成熟和中性脂质积累的影响，卵丘细胞和植入前胚胎中脂质相关转录物的表达。
■将来自人和绵羊卵巢的原代卵泡膜细胞培养物暴露于TBT，TPT,或DBT（1、10或50ng/ml）。这些化学物质对中性脂质积累的影响，脂质丰度和组成，脂质稳态相关基因表达，使用液相色谱-质谱（LC-MS）评估细胞因子的分泌，基于抑制剂的方法，细胞因子分泌，和脂质本体论分析。我们还将鼠卵丘-卵母细胞复合物暴露于TBT并评估卵母细胞成熟，胚胎发育,卵丘细胞和胚泡中与脂质稳态相关的mRNA表达。
■暴露于TBT导致人和绵羊原代卵泡膜细胞中更高的细胞内中性脂质。在绵羊卵泡膜细胞中，这种效应是剂量依赖性的，独立于细胞阶段，部分由LXR介导。与TBT相比，DBT和TPT导致更高的细胞内中性脂质，但程度较低。在暴露于TBT的人卵泡膜细胞中，超过140种脂质和9种细胞因子失调。与脂肪生成和脂肪酸合成相关的基因在卵泡膜细胞中表达较高，以及暴露于TBT的卵丘细胞和胚泡。然而,TBT不影响卵母细胞成熟或胚泡发育的速率。
■TBT诱导人和绵羊卵泡膜细胞血脂异常，这可能是在TBT暴露的啮齿动物模型中报告的一些TBT诱导的生育力失调的原因。https://doi.org/10.1289/EHP13955.
■我们调查了有机锡[TBT，TPT,或二丁基锡（DBT）]诱导卵巢卵泡膜细胞中的脂质失调以及肝X受体（LXR）在这种作用中的作用。我们还测试了TBT对卵母细胞成熟和中性脂质积累的影响，卵丘细胞和植入前胚胎中脂质相关转录物的表达。
■将来自人和绵羊卵巢的原代卵泡膜细胞培养物暴露于TBT，TPT,或DBT（1、10或50ng/ml）。这些化学物质对中性脂质积累的影响，脂质丰度和组成，脂质稳态相关基因表达，使用液相色谱-质谱（LC-MS）评估细胞因子的分泌，基于抑制剂的方法，细胞因子分泌，和脂质本体论分析。我们还将鼠卵丘-卵母细胞复合物暴露于TBT并评估卵母细胞成熟，胚胎发育,卵丘细胞和胚泡中与脂质稳态相关的mRNA表达。
■暴露于TBT导致人和绵羊原代卵泡膜细胞中更高的细胞内中性脂质。在绵羊卵泡膜细胞中，这种效应是剂量依赖性的，独立于细胞阶段，部分由LXR介导。与TBT相比，DBT和TPT导致更高的细胞内中性脂质，但程度较低。在暴露于TBT的人卵泡膜细胞中，超过140种脂质和9种细胞因子失调。与脂肪生成和脂肪酸合成相关的基因在卵泡膜细胞中表达较高，以及暴露于TBT的卵丘细胞和胚泡。然而,TBT不影响卵母细胞成熟或胚泡发育的速率。
■TBT诱导人和绵羊卵泡膜细胞血脂异常，这可能是在TBT暴露的啮齿动物模型中报告的一些TBT诱导的生育力失调的原因。https://doi.org/10.1289/EHP13955.
