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Impact of In Vitro Long-Term Low-Level DEHP Exposure on Gene Expression Profile in Human Granulosa Cells

Here, we applied a model of long-term exposure of human granulosa cells to low environmentally relevant levels of di(2-ethylhexyl) phthalate (DEHP). This approach provides more relevant data regarding the impact of DEHP on the function of human granulosa cells. The immortalized human granulosa cells...

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Autores principales: Nenadov, Dragana Samardzija, Pogrmic-Majkic, Kristina, Tesic, Biljana, Kokai, Dunja, Fa Nedeljkovic, Svetlana, Stanic, Bojana, Andric, Nebojsa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332775/
https://www.ncbi.nlm.nih.gov/pubmed/35892601
http://dx.doi.org/10.3390/cells11152304
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author Nenadov, Dragana Samardzija
Pogrmic-Majkic, Kristina
Tesic, Biljana
Kokai, Dunja
Fa Nedeljkovic, Svetlana
Stanic, Bojana
Andric, Nebojsa
author_facet Nenadov, Dragana Samardzija
Pogrmic-Majkic, Kristina
Tesic, Biljana
Kokai, Dunja
Fa Nedeljkovic, Svetlana
Stanic, Bojana
Andric, Nebojsa
author_sort Nenadov, Dragana Samardzija
collection PubMed
description Here, we applied a model of long-term exposure of human granulosa cells to low environmentally relevant levels of di(2-ethylhexyl) phthalate (DEHP). This approach provides more relevant data regarding the impact of DEHP on the function of human granulosa cells. The immortalized human granulosa cells HGrC1 were exposed to 50 nM and 250 nM DEHP for four weeks. The cells were collected every week to analyze the basal granulosa cells’ functions. A portion of the DEHP-exposed cells was stimulated with forskolin (FOR) for 48 h. Steroidogenesis was investigated using ELISA, whereas DNBQ sequencing and RT-qPCR were used to analyze gene expression. The results show that steroidogenesis was not affected by DEHP exposure. RNAsequencing shows that DEHP caused week- and concentration-specific changes in various genes and functions in HGrC1. Sulfotransferase family 1A member 3 (SULT1A3) and 4 (SULT1A4), which are involved in catecholamine metabolism, were the most prominent genes affected by DEHP under both the basal and FOR-stimulated conditions in all four weeks of exposure. This study showed, for the first time, that SULT1A3 and SULT1A4 are expressed in human granulosa cells, are regulated by FOR, and are affected by low-level DEHP exposure. These data provide new insight into the relationship between DEHP, SULT1A3, and SULT1A4 in human granulosa cells.
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spelling pubmed-93327752022-07-29 Impact of In Vitro Long-Term Low-Level DEHP Exposure on Gene Expression Profile in Human Granulosa Cells Nenadov, Dragana Samardzija Pogrmic-Majkic, Kristina Tesic, Biljana Kokai, Dunja Fa Nedeljkovic, Svetlana Stanic, Bojana Andric, Nebojsa Cells Article Here, we applied a model of long-term exposure of human granulosa cells to low environmentally relevant levels of di(2-ethylhexyl) phthalate (DEHP). This approach provides more relevant data regarding the impact of DEHP on the function of human granulosa cells. The immortalized human granulosa cells HGrC1 were exposed to 50 nM and 250 nM DEHP for four weeks. The cells were collected every week to analyze the basal granulosa cells’ functions. A portion of the DEHP-exposed cells was stimulated with forskolin (FOR) for 48 h. Steroidogenesis was investigated using ELISA, whereas DNBQ sequencing and RT-qPCR were used to analyze gene expression. The results show that steroidogenesis was not affected by DEHP exposure. RNAsequencing shows that DEHP caused week- and concentration-specific changes in various genes and functions in HGrC1. Sulfotransferase family 1A member 3 (SULT1A3) and 4 (SULT1A4), which are involved in catecholamine metabolism, were the most prominent genes affected by DEHP under both the basal and FOR-stimulated conditions in all four weeks of exposure. This study showed, for the first time, that SULT1A3 and SULT1A4 are expressed in human granulosa cells, are regulated by FOR, and are affected by low-level DEHP exposure. These data provide new insight into the relationship between DEHP, SULT1A3, and SULT1A4 in human granulosa cells. MDPI 2022-07-27 /pmc/articles/PMC9332775/ /pubmed/35892601 http://dx.doi.org/10.3390/cells11152304 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nenadov, Dragana Samardzija
Pogrmic-Majkic, Kristina
Tesic, Biljana
Kokai, Dunja
Fa Nedeljkovic, Svetlana
Stanic, Bojana
Andric, Nebojsa
Impact of In Vitro Long-Term Low-Level DEHP Exposure on Gene Expression Profile in Human Granulosa Cells
title Impact of In Vitro Long-Term Low-Level DEHP Exposure on Gene Expression Profile in Human Granulosa Cells
title_full Impact of In Vitro Long-Term Low-Level DEHP Exposure on Gene Expression Profile in Human Granulosa Cells
title_fullStr Impact of In Vitro Long-Term Low-Level DEHP Exposure on Gene Expression Profile in Human Granulosa Cells
title_full_unstemmed Impact of In Vitro Long-Term Low-Level DEHP Exposure on Gene Expression Profile in Human Granulosa Cells
title_short Impact of In Vitro Long-Term Low-Level DEHP Exposure on Gene Expression Profile in Human Granulosa Cells
title_sort impact of in vitro long-term low-level dehp exposure on gene expression profile in human granulosa cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332775/
https://www.ncbi.nlm.nih.gov/pubmed/35892601
http://dx.doi.org/10.3390/cells11152304
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