Tire rubber-derived contaminants 6PPD and 6PPD-quinone reduce attachment and outgrowth of trophoblast spheroids onto endometrial epithelial cells
N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD), a synthetic additive widely used in the rubber industry, and its oxidized product 6PPD-quinone (6PPDQ), have garnered widespread attention as an emerging hazardous chemicals owing to their potential detrimental effects on aquatic ecosystem a...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325000806 |
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| author | Jong Geol Lee Seon Min Lee Moonjung Hyun Jeong Doo Heo |
| author_facet | Jong Geol Lee Seon Min Lee Moonjung Hyun Jeong Doo Heo |
| author_sort | Jong Geol Lee |
| collection | DOAJ |
| description | N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD), a synthetic additive widely used in the rubber industry, and its oxidized product 6PPD-quinone (6PPDQ), have garnered widespread attention as an emerging hazardous chemicals owing to their potential detrimental effects on aquatic ecosystem and human health. The effects of 6PPD and 6PPDq on the female reproductive tract, especially embryo implantation, remain unknown and were investigated in this study. We used the spheroid attachment and outgrowth models of BeWo trophoblastic spheroids and Ishikawa cells as surrogates for the human blastocyst and endometrial epithelium, respectively. Treatment with the chemicals for up to 48 h decreased the viability of the cells in a dose- and cell line-dependent manner (20–100 μM 6PPD and 10–100 μM 6PPDQ for both the cell lines). At a noncytotoxic concentration, exposure of Ishikawa cells to 1 and 10 μM 6PPD reduced the attachment of BeWo spheroids and further inhibited their invasion and outgrowth on the endometrial epithelial monolayer. A similar result was observed in 1 μM 6PPDQ-exposed groups. Gene expression profiling of 6PPD- and 6PPDQ-exposed endometrial epithelial cells revealed that both 6PPD and 6PPDQ differentially regulated a panel of transcript markers toward overall downregulation of receptivity and invasion. The study provides the first proof of the adverse effects of 6PPD and 6PPDQ on human endometrial receptivity and trophoblast invasion during the window of implantation, warranting the need for further in vivo and clinical studies. |
| format | Article |
| id | doaj-art-c9ca85f34b2c449d87507df6a276f388 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-c9ca85f34b2c449d87507df6a276f3882025-02-12T05:30:10ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01290117744Tire rubber-derived contaminants 6PPD and 6PPD-quinone reduce attachment and outgrowth of trophoblast spheroids onto endometrial epithelial cellsJong Geol Lee0Seon Min Lee1Moonjung Hyun2Jeong Doo Heo3Center for Bio-Health Research, Division of Gyeongnam Bio-Environmental Research, Korea Institute of Toxicology, Jinju 52834, Republic of Korea; Corresponding authors.Center for Bio-Health Research, Division of Gyeongnam Bio-Environmental Research, Korea Institute of Toxicology, Jinju 52834, Republic of KoreaCenter for Bio-Health Research, Division of Gyeongnam Bio-Environmental Research, Korea Institute of Toxicology, Jinju 52834, Republic of KoreaKorea Institute of Toxicology, Daejeon 34114, Republic of Korea; Corresponding authors.N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD), a synthetic additive widely used in the rubber industry, and its oxidized product 6PPD-quinone (6PPDQ), have garnered widespread attention as an emerging hazardous chemicals owing to their potential detrimental effects on aquatic ecosystem and human health. The effects of 6PPD and 6PPDq on the female reproductive tract, especially embryo implantation, remain unknown and were investigated in this study. We used the spheroid attachment and outgrowth models of BeWo trophoblastic spheroids and Ishikawa cells as surrogates for the human blastocyst and endometrial epithelium, respectively. Treatment with the chemicals for up to 48 h decreased the viability of the cells in a dose- and cell line-dependent manner (20–100 μM 6PPD and 10–100 μM 6PPDQ for both the cell lines). At a noncytotoxic concentration, exposure of Ishikawa cells to 1 and 10 μM 6PPD reduced the attachment of BeWo spheroids and further inhibited their invasion and outgrowth on the endometrial epithelial monolayer. A similar result was observed in 1 μM 6PPDQ-exposed groups. Gene expression profiling of 6PPD- and 6PPDQ-exposed endometrial epithelial cells revealed that both 6PPD and 6PPDQ differentially regulated a panel of transcript markers toward overall downregulation of receptivity and invasion. The study provides the first proof of the adverse effects of 6PPD and 6PPDQ on human endometrial receptivity and trophoblast invasion during the window of implantation, warranting the need for further in vivo and clinical studies.http://www.sciencedirect.com/science/article/pii/S01476513250008066PPD6PPDQEndometrial receptivityTrophoblast invasionSpheroid attachmentSpheroid outgrowth |
| spellingShingle | Jong Geol Lee Seon Min Lee Moonjung Hyun Jeong Doo Heo Tire rubber-derived contaminants 6PPD and 6PPD-quinone reduce attachment and outgrowth of trophoblast spheroids onto endometrial epithelial cells Ecotoxicology and Environmental Safety 6PPD 6PPDQ Endometrial receptivity Trophoblast invasion Spheroid attachment Spheroid outgrowth |
| title | Tire rubber-derived contaminants 6PPD and 6PPD-quinone reduce attachment and outgrowth of trophoblast spheroids onto endometrial epithelial cells |
| title_full | Tire rubber-derived contaminants 6PPD and 6PPD-quinone reduce attachment and outgrowth of trophoblast spheroids onto endometrial epithelial cells |
| title_fullStr | Tire rubber-derived contaminants 6PPD and 6PPD-quinone reduce attachment and outgrowth of trophoblast spheroids onto endometrial epithelial cells |
| title_full_unstemmed | Tire rubber-derived contaminants 6PPD and 6PPD-quinone reduce attachment and outgrowth of trophoblast spheroids onto endometrial epithelial cells |
| title_short | Tire rubber-derived contaminants 6PPD and 6PPD-quinone reduce attachment and outgrowth of trophoblast spheroids onto endometrial epithelial cells |
| title_sort | tire rubber derived contaminants 6ppd and 6ppd quinone reduce attachment and outgrowth of trophoblast spheroids onto endometrial epithelial cells |
| topic | 6PPD 6PPDQ Endometrial receptivity Trophoblast invasion Spheroid attachment Spheroid outgrowth |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325000806 |
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