Evaluation of Lipids and Lipid-Related Transcripts in Human and Ovine Theca Cells and an in Vitro Mouse Model Exposed to the Obesogen Chemical Tributyltin.
BACKGROUND: 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 t...
| Publicado en: | Environmental Health Perspectives Vol. 132; no. 4; pp. 047009-1 - 47027 |
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| Autores principales: | , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
National Institute of Environmental Health Sciences
Apr2024
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=177145079&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 177145079 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00916765 3B5 jtl: Environmental Health Perspectives issn: 00916765 maglogo: N pubinfo: dt: Apr2024 vid: 132 iid: 4 pid: 56539 pub: National Institute of Environmental Health Sciences place: Research Triangle Park, North Carolina artinfo: ui: 177145079 177145079 177145079 10.1289/EHP13955 177145079 ppf: 047009-1 ppct: 18 formats: tig: atl: Evaluation of Lipids and Lipid-Related Transcripts in Human and Ovine Theca Cells and an in Vitro Mouse Model Exposed to the Obesogen Chemical Tributyltin. aug: au: Pascuali, Natalia Yong Pu Waye, Anita A. Pearl, Sarah Martin, Denny Sutton, Allison Shikanov, Ariella Veiga-Lopez, Almudena affil: Department of Pathology, University of Illinois Chicago, Chicago, Illinois, USA sug: subj: Lipids Drug Effects Obesity Chemically Induced Models, Biological Organic Chemicals Adverse Effects Ovarian Follicle Drug Effects Environmental Exposure Adverse Effects Ovum Drug Effects Gene Expression Drug Effects Blastocyst Drug Effects Animal Studies Mice Human In Vitro Studies Cell Culture Techniques Organic Chemicals Administration and Dosage Homeostasis Drug Effects Cytokines Drug Effects Liquid Chromatography-Mass Spectrometry RNA, Messenger Drug Effects Blastomeres Drug Effects Cell Proliferation Drug Effects Polymerase Chain Reaction Metabolomics Cell Migration Assays Tissue and Organ Harvesting Fertilization in Vitro Descriptive Statistics Two-Way Analysis of Variance Post Hoc Analysis T-Tests Data Analysis Software Lipids Metabolism Funding Source Hyperlipidemia Risk Factors ab: BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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