Table 3.
Effects of Bisphenol A (BPA) in Placental In Vitro Models
| Cell Model | µM BPAa | Treatment Length (h) | Summary of Outcomes | Ref. |
|---|---|---|---|---|
| JEG-3 | 25 | 10 min, 30 min, 1, 2 | Effects on aromatase activity: YES | Nativelle-Serpentini et al. (2003) |
| 18 | Effects on aromatase activity: YES | |||
| 50 | 10 min | Effects on aromatase activity/mRNA: NO | ||
| 30 min, 1 | Effects on aromatase activity: NO | |||
| 2 | Effects on aromatase activity: YES | |||
| 18 | Effects on aromatase activity: YES | |||
| 100 | 10 min, 2 | Effects on aromatase activity: YES | ||
| 30 min, 1 | Effects on aromatase activity: NO | |||
| 18 | Effects on aromatase activity: YES | |||
| BeWo | 0.1, 10, 50 | approximately 1 | Effects on measure of drug efflux: YES | Jin and Audus (2005) |
| Microsomes @term | 500 | 15 min | Effects on aromatase activity: YES | Benachour et al. (2007) |
| 1° Cytotrophoblasts | 8.8×10−4, 8.8×10−3 | 24 | Effects on measure of apoptosis: NO, necrosis: YES, TNF-α mRNA: YES, TNF-α prot: NO | Benachour and Aris (2009) |
| 0.0876, 0.438 | Effects on measure of apoptosis: YES, necrosis: YES, TNF-α mRNA: YES, TNF-α prot: YES | |||
| 0.876 | Effects on measure of apoptosis: YES, necrosis: NO, TNF-α mRNA: NO, TNF-α prot: NO | |||
| 8.76, 87.6 | Effects on measure of apoptosis: YES, necrosis NO, TNF-α mRNA: NO, TNF-α prot: YES | |||
| 438, 876 | Effects on measure of apoptosis: YES, necrosis YES, TNF-α mRNA: NO, TNF-α prot: YES | |||
| JEG-3 | 1 | 24 | Effects on aromatase mRNA/protein expression or promoter activity, aromatase activity: NO | Huang and Leung (2009) |
| PL30 | Effect on aromatase mRNA: NO | |||
| JEG-3 | 5 | Effects on aromatase mRNA/protein expression or promoter activity, aromatase activity: YES | ||
| PL30 | Effect on aromatase mRNA: NO | |||
| JEG-3 | 25 | Effects on aromatase mRNA/protein expression or promoter activity, aromatase activity: YES | ||
| PL30 | Effect on aromatase mRNA: YES | |||
| JEG-3 | 50 | Effects on aromatase mRNA/protein expression or promoter activity, aromatase activity: YES | ||
| PL30 | Effect on aromatase mRNA: YES | |||
| JEG-3, PL30 | 100 | Effects on aromatase mRNA/protein expression or promoter activity, aromatase activity: YES | ||
| 3A, HTR-8/Svneo | 1.095 | 6 days | Effects on miR-146a expression: NO | Avissar-Whiting et al. (2010) |
| 3A | 10.95 | Effects on miR-146a expression/survival after miR-146a overexpression: NO | ||
| HTR-8/Svneo | Effects on miR-146a expression: NO | |||
| 3A | 109.51 | Effects on miR-146a and other miR expression: YES; altered survival after miR-146a overexpression: NO | ||
| TCL-1 | Effects on miR expression: NO | |||
| HTR-8/Svneo | Effects on miR-146a and other miR expression: YES | |||
| JEG-3 | 1×10−3 | 24 | Effects on proliferation: NO (also in BeWo cells) | Morice et al. (2011) |
| 48 | Effects on viability or proliferation: NO (also in BeWo cells) | |||
| 0.01 | 24 | Effects on proliferation: NO (also in BeWo cells) | ||
| 48 | Effects on viability or proliferation: NO (also in BeWo cells) | |||
| 0.1 | 1 or 6? | Effects on mRNA of cell cycle-related genes: SOME | ||
| 8 | Effects on mRNA of an apoptosis-related gene: YES | |||
| 24 | Effects on proliferation: YES (NO in BeWo) | |||
| 48 | Effect on viability: NO, apoptosis: YES, proliferation: YES (NO in BeWo) | |||
| 1 | 1 or 6? | Effects on mRNA of cell cycle-related genes: SOME | ||
| 8 | Effects on mRNA of an apoptosis-related gene: YES | |||
| 24 | Effects on proliferation: YES (NO in BeWo)—potentially through Errγ | |||
| 48 | Effects on proliferation: YES (NO in BeWo), viability: NO, apoptosis: YES | |||
| 10 | 24 | Effects on proliferation: YES (NO in BeWo); | ||
| 48 | Effects on proliferation: YES (NO in BeWo), viability: NO | |||
| 100 | 48 | Effects on viability: YES | ||
| JEG-3 | 1, 5 | 24 | Effects on CRH mRNA/protein expression and promoter activity: NO, upstream proteins: SOME | Huang and Leung (2012)b |
| 25 | Effects on CRH mRNA/protein expression and promoter activity: YES, upstream proteins: SOME | |||
| 50 | Effects on CRH mRNA/protein expression and promoter activity: YES, upstream proteins: YES | |||
| 1° Villi | 5×10−4 | 24 | Effect on β-hCG in media with/without BPA-conditioned decidualized stromal cells (DSCs): NO;Effect on proinflammatory cytokine MIF: YES—not if co-cultured with BPA-conditioned DSCs | Mannelli et al. (2014) |
| 48 | Effect on β-hCG in media with/without BPA-conditioned decidualized stromal cells (DSCs): NO | |||
| BeWo | 0.01 | 48 | Effect on proliferation: NO, invasion into endometrial cells YES; invasion-related mRNA/prot: YES, DNA methylation-related mRNA/prot: SOME | Wang et al. (2015) |
| 0.1 | Effect on proliferation: NO | |||
| 1 | Effect on proliferation: YES, invasion into endometrial cells: YES; invasion-related mRNA/prot: YES, DNA methylation-related mRNA/prot: SOME | |||
| 10 | Effect on proliferation: YES, invasion-related prot: YES, DNA methylation-related mRNA/prot: SOME | |||
| 100 | Effect on proliferation: NO, invasion into endometrial cells: YES, invasion-related mRNA/prot: YES, DNA methylation-related mRNA/prot: YES | |||
| 1000 | Effect on proliferation: YES | |||
| 1° Trophoblasts | 0.438 | 24 | Effects on 11B-HSD2 activity, mRNA, prot: NO | Rajakumar et al. (2015) |
| 1.095, 2.19, 4.38 | 24 | Effects on 11B-HSD2 activity, mRNA, prot: YES | ||
| 8.76 | 3 | Effects on 11B-HSD2 activity, mRNA, prot: NO | ||
| 6, 12 | Effects on 11B-HSD2 activity, mRNA, prot: YES | |||
| 24 | Effects on 11B-HSD2 activity, mRNA, prot: YES Effects on nutrient transport- and hormone-related mRNA: YES |
|||
| HTR-8/Svneo | 1×10−9 | 24, 48 | Effect on viability: NO, proliferation: NO, migration: NO, invasion: NO, DNA content: NO | Spagnoletti et al. (2015) |
| 72 | Effect on viability: NO, proliferation: NO, migration: NO, invasion: NO, DNA content: YES | |||
| 1×10−7 | 24, 48 | Effect on viability: NO, proliferation: NO, migration: NO, invasion: NO, DNA content: YES | ||
| 72 | Effect on viability: NO, proliferation: NO, migration: NO, invasion: YES, DNA content: YES | |||
| 1×10−5 | 24 | Effect on viability: NO, proliferation: NO, migration: NO, invasion: NO, DNA content: NO, interaction w/ HUVECs: NO | ||
| 48 | Effect on viability: NO, proliferation: NO, migration: YES, invasion: YES, DNA content: YES (not reversed by ICI), interaction w/ HUVECs: NO | |||
| 72 | Effect on viability: NO, proliferation: NO, migration: YES, invasion: YES, DNA content: YES; differentiation: NO, cell cycle-related protein: NO | |||
| 1×10−3 | 24 | Effect on viability: NO, proliferation: NO, migration: NO, invasion: NO, DNA content: NO | ||
| 48 | Effect on viability: NO, proliferation: NO, migration: YES, invasion: YES, DNA content: YES | |||
| 72 | Effect on viability: NO, proliferation: NO, migration: YES, invasion: YES, DNA content: YES; differentiation: YES, cell cycle-related protein: YES | |||
| 0.1 | 24 | Effect on viability: NO, proliferation: NO, migration: NO, invasion: NO, DNA content: NO | ||
| 48 | Effect on viability: NO, proliferation: NO, migration: YES, invasion: YES, DNA content: YES | |||
| 72 | Effect on viability: NO, proliferation: NO, migration: YES, invasion: YES, DNA content: YES; differentiation: YES, cell cycle-related protein: NO | |||
| 1° in first trimester | 1×10−3 | 24, 48 | Effects on chemical efflux-related protein: NO | Sieppi et al. (2016) |
| 1° at term | 24 | Effects on chemical efflux-related protein/mRNA: NO | ||
| 48 | Effects on chemical efflux-related protein: YES—partly reversed by ICI mRNA: NO | |||
| 1° in first trimester | 0.1 | 24, 48 | Effects on chemical efflux-related protein: NO | |
| 1° at term | 24 | Effects on chemical efflux-related protein: NO; mRNA: YES | ||
| 48 | Effects on chemical efflux-related protein/mRNA: NO | |||
| JEG-3 | 0.01–500 | 24 | Effects on cytotoxicity at 138–218 μM: YES; ROS generation: YES; aromatase activity at IC50=71 μM: YES | Perez-Albaladejo et al. (2017) |
| HTR-8/Svneo | 0.1 | 24 | Effects on migration: NO | Lan et al. (2017) |
| 1, 10, 50 | Effects on migration: YES | |||
| 0.1 | 48 | Effects on proliferation: NO, migration: YES; invasion-related proteins: NO; adhesion-related protein: YES (NO mRNA), mesenchymal proteins/mRNA: NO | ||
| 1 | Effects on proliferation: NO, migration: YES; invasion-related proteins: SOME; adhesion-related protein: YES (NO mRNA), mesenchymal proteins/mRNA: NO. Effects potentially through ERK signaling | |||
| 10, 50 | Effects on proliferation: NO, migration: YES; invasion-related proteins: YES; adhesion-related protein and mRNA: YES, mesenchymal proteins/mRNA: NO | |||
| 1° villi in first trimester | 50 | 48, 72 | Effects on migration: YES; adhesion-related protein: NO |
a
Doses from studies were converted to μM to facilitate comparison across studies.
b
Authors also reported increased binding of CRE at the CRH promoter and CREB phosphorylation by BPA, but quantified data were not presented to include in this dose-response table.