Testosterone-Mediated Endocrine Function and TH1/TH2 Cytokine Balance after Prenatal Exposure to Perfluorooctane Sulfonate: By Sex Status
Abstract
:1. Introduction
2. Results
2.1. Body and Organ Mass/Serum PFOS Concentrations
2.2. Splenic and Thymic Cellularity
2.3. Lymphocyte Immunophenotypes
2.4. Lymphocyte Proliferation
2.5. NK Cell Function
2.6. Splenic Plaque-Forming Cell Levels
2.7. Ex Vivo Splenocyte Spontaneous IL-2, IL-4, IL-10 and IFNγ Production
2.8. Serum Hormone Levels
2.9. Interaction between Sex and PFOS Exposure
3. Discussion
4. Materials and Methods
4.1. Ethics Statement
4.2. Chemicals, Antibodies and Supplies
4.3. Animals and Treatments
4.4. Serum Sampling, Body and Organ Mass and Organ Cellularity
4.5. Serum PFOS Analysis
4.6. Serum Hormone Levels
4.7. Lymphocyte Proliferation Assay
4.8. Splenic and Thymic CD4/CD8 Sub-Population Measurements
4.9. Natural Killer Cell Activity
4.10. Antibody Plaque-Forming Cell Assay
4.11. Measures of Spontaneous ex Vivo IL-2, IL-4, IL-10 and IFNγ
4.12. Statistics
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
POP | Persistent organic pollutant |
PFOS | Perfluorooctane sulfonate |
PFASs | polyfluoroalkyl substances |
SRBC | Sheep red blood cells |
GPC | Guinea pig complement |
LDH | Lactate dehydrogenase |
PFC | Plaque-forming cells |
NK | Natural killer |
TH | T-helper |
IFNγ | Interferon-γ |
IL-2 | Interleukin-2 |
IL-4 | Interleukin-4 |
IL-10 | Interleukin-10 |
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Sex | PFOS Gestational Exposure Level (mg/kg/day) | ||||
---|---|---|---|---|---|
0.0 (Control) | 0.1 | 1.0 | 5.0 | ||
4 weeks of age | |||||
Body weight (g) | Male | 16.13 ± 0.63 | 16.59 ± 0.75 | 14.70 ± 0.58 | 14.37 ± 0.62 |
Female | 14.33 ± 0.37 | 14.16 ± 0.49 | 13.52 ± 0.31 | 13.28 ± 0.40 | |
Spleen b | Male | 0.53 ± 0.04 | 0.49 ± 0.03 | 0.45 ± 0.05 | 0.42 ± 0.02 a |
Female | 0.51 ± 0.03 | 0.48 ± 0.02 | 0.47 ± 0.04 | 0.45 ± 0.02 | |
Thymus b | Male | 0.61 ± 0.05 | 0.54 ± 0.04 | 0.58 ± 0.03 | 0.49 ± 0.02 a |
Female | 0.57 ± 0.03 | 0.59 ± 0.02 | 0.54 ± 0.02 | 0.51 ± 0.01 | |
Kidney b | Male | 1.70 ± 0.05 | 1.74 ± 0.03 | 1.82 ± 0.04 | 1.76 ± 0.05 |
Female | 1.67 ± 0.04 | 1.61 ± 0.05 | 1.74 ± 0.03 | 1.65 ± 0.04 | |
Liver b | Male | 7.21 ± 0.14 | 6.97 ± 0.21 | 7.75 ± 0.17 | 8.16 ± 0.24 a |
Female | 6.88 ± 0.15 | 6.65 ± 0.25 | 7.04 ± 0.22 | 7.59 ± 0.30 a | |
Serum PFOS concentration (mg/L) | |||||
Male | 0.05 ± 0.01 | 6.38 ± 0.35 | 47.03 ± 3.23 a | 118.40 ± 6.27 a | |
Female | 0.04 ± 0.01 | 5.16 ± 0.27 | 41.81 ± 3.62 a | 107.53 ± 4.51 a | |
8 weeks of age | |||||
Body weight (g) | Male | 23.04 ± 0.75 | 24.96 ± 0.64 | 25.12 ± 0.96 | 23.48 ± 0.43 |
Female | 21.51 ± 0.91 | 22.84 ± 0.67 | 20.65 ± 0.59 | 19.37 ± 0.73 | |
Spleen b | Male | 0.42 ± 0.03 | 0.37 ± 0.05 | 0.43 ± 0.02 | 0.32 ± 0.03 |
Female | 0.45 ± 0.02 | 0.46 ± 0.03 | 0.41 ± 0.03 | 0.43 ± 0.04 | |
Thymus b | Male | 0.30 ± 0.01 | 0.27 ± 0.02 | 0.29 ± 0.01 | 0.24 ± 0.03 a |
Female | 0.33 ± 0.02 | 0.31 ± 0.03 | 0.36 ± 0.02 | 0.32 ± 0.01 | |
Kidney b | Male | 1.59 ± 0.04 | 1.61 ± 0.03 | 1.68 ± 0.03 | 1.54 ± 0.06 |
Female | 1.43 ± 0.11 | 1.57 ± 0.05 | 1.38 ± 0.04 | 1.46 ± 0.03 | |
Liver b | Male | 6.60 ± 0.18 | 6.41 ± 0.14 | 7.05 ± 0.21 | 6.39 ± 0.17 |
Female | 5.77 ± 0.21 | 5.94 ± 0.13 | 6.03 ± 0.07 | 5.82 ± 0.09 | |
Serum PFOS concentration (mg/L) | |||||
Male | 0.04 ± 0.01 | 3.79 ± 0.26 | 37.53 ± 3.96 a | 82.66 ± 4.18 a | |
Female | 0.04 ± 0.01 | 3.04 ± 0.17 | 31.17 ± 2.59 a | 71.68 ± 4.49 a |
Sex | PFOS (mg/kg/day) | CD8+ (Cells × 106) | DP (Cells × 105) | CD4+ (Cells × 107) | B220 (Cells × 107) |
---|---|---|---|---|---|
4 weeks of age | |||||
Male | 0.0 (Control) | 10.62 ± 0.61 | 5.24 ± 0.94 | 2.21 ± 0.18 | 5.98 ± 0.41 |
0.1 | 10.86 ± 0.55 | 5.63 ± 0.37 | 2.06 ± 0.13 | 5.65 ± 0.35 | |
1.0 | 9.98 ± 0.43 | 6.76 ± 0.68 | 1.85 ± 0.25 | 5.14 ± 0.26 | |
5.0 | 8.49 ± 0.36 a | 6.48 ± 0.42 | 1.64 ± 0.09 a | 4.73 ± 0.21 a | |
Female | 0.0 (Control) | 9.18 ± 0.67 | 4.51 ± 0.53 | 1.94 ± 0.33 | 5.44 ± 0.31 |
0.1 | 9.44 ± 0.58 | 5.76 ± 0.46 | 1.67 ± 0.32 | 5.62 ± 0.25 | |
1.0 | 8.59 ± 0.34 | 5.14 ± 0.70 | 1.74 ± 0.46 | 5.09 ± 0.19 | |
5.0 | 8.80 ± 0.75 | 4.28 ± 0.64 | 1.43 ± 0.27 | 4.47 ± 0.27 a | |
8 weeks of age | |||||
Male | 0.0 | 5.69 ± 0.36 | 1.81 ± 0.60 | 1.77 ± 0.09 | 6.43 ± 0.25 |
0.1 | 6.07 ± 0.25 | 1.77 ± 0.28 | 1.54 ± 0.11 | 6.17 ± 0.28 | |
1.0 | 6.31 ± 0.30 | 2.14 ± 0.26 | 1.60 ± 0.08 | 5.90 ± 0.24 | |
5.0 | 5.78 ± 0.42 | 1.62 ± 0.19 | 1.37 ± 0.10 a | 5.74 ± 0.30 | |
Female | 0.0 | 5.40 ± 0.34 | 1.69 ± 0.24 | 1.63 ± 0.14 | 4.41 ± 0.15 |
0.1 | 5.64 ± 0.45 | 1.78 ± 0.35 | 1.59 ± 0.13 | 4.64 ± 0.23 | |
1.0 | 6.01 ± 0.62 | 1.94 ± 0.58 | 1.46 ± 0.09 | 4.22 ± 0.19 | |
5.0 | 5.27 ± 0.33 | 1.61 ± 0.22 | 1.32 ± 0.07 | 3.17 ± 0.27 a |
Sex | PFOS (mg/kg/day) | CD8+ (Cells × 107) | DP (Cells × 105) | DN (Cells × 107) | CD4+ (Cells × 107) |
---|---|---|---|---|---|
4 weeks of age | |||||
Male | 0.0 | 5.14 ± 0.18 | 12.55 ± 0.71 | 7.44 ± 0.42 | 1.78 ± 0.09 |
0.1 | 4.93 ± 0.22 | 11.92 ± 0.76 | 8.65 ± 0.31 | 1.84 ± 0.12 | |
1.0 | 4.66 ± 0.37 | 13.08 ± 0.82 | 6.46 ± 0.72 | 1.51 ± 0.11 | |
5.0 | 4.43 ± 0.29 | 12.14 ± 0.63 | 5.77 ± 0.50 a | 1.37 ± 0.06 a | |
Female | 0.0 | 3.59 ± 0.34 | 10.79 ± 0.94 | 6.98 ± 0.68 | 1.58 ± 0.12 |
0.1 | 3.67 ± 0.51 | 10.84 ± 0.57 | 7.15 ± 0.40 | 1.75 ± 0.09 | |
1.0 | 4.21 ± 0.47 | 10.56 ± 0.43 | 6.43 ± 0.51 | 1.61 ± 0.13 | |
5.0 | 3.45 ± 0.26 | 10.61 ± 0.30 | 6.09 ± 0.32 | 1.39 ± 0.14 | |
8 weeks of age | |||||
Male | 0.0 | 4.01 ± 0.35 | 9.11 ± 1.03 | 5.16 ± 0.54 | 1.87 ± 0.08 |
0.1 | 4.37 ± 0.42 | 9.25 ± 0.67 | 6.05 ± 0.67 | 1.71 ± 0.07 | |
1.0 | 3.52 ± 0.37 | 8.66 ± 1.24 | 5.13 ± 0.39 | 1.60 ± 0.14 | |
5.0 | 3.71 ± 0.41 | 8.30 ± 1.38 | 4.95 ± 0.44 | 1.53 ± 0.10 a | |
Female | 0.0 | 3.64 ± 0.43 | 8.79 ± 0.75 | 4.65 ± 0.31 | 1.66 ± 0.11 |
0.1 | 3.51 ± 0.57 | 8.65 ± 0.69 | 5.03 ± 0.28 | 1.58 ± 0.16 | |
1.0 | 3.79 ± 0.36 | 7.72 ± 0.58 | 4.50 ± 0.24 | 1.69 ± 0.10 | |
5.0 | 3.22 ± 0.40 | 7.93 ± 1.25 | 5.49 ± 0.48 | 1.47 ± 0.08 |
Sex | PFOS | IL-2 | IFNγ | IL-4 | IL-10 |
---|---|---|---|---|---|
4 weeks of age | |||||
Male | 0.0 | 54.02 ± 4.20 | 24.67 ± 2.53 | 11.87 ± 2.02 | 53.21 ± 4.32 |
0.1 | 51.89 ± 5.21 | 22.38 ± 2.05 | 13.95 ± 1.35 | 57.75 ± 3.97 | |
1.0 | 47.08 ± 3.14 | 20.03 ± 1.70 | 15.81 ± 1.92 | 54.68 ± 4.21 | |
5.0 | 38.49 ± 3.68 a | 19.63 ± 1.53 | 17.78 ± 1.23 a | 60.61 ± 3.64 | |
Female | 0.0 | 49.65 ± 4.01 | 22.07 ± 2.28 | 13.55 ± 1.85 | 49.45 ± 4.31 |
0.1 | 46.50 ± 3.07 | 24.90 ± 2.14 | 15.61 ± 1.09 | 53.96 ± 5.53 | |
1.0 | 41.45 ± 3.98 | 20.47 ± 1.79 | 17.59 ± 1.37 | 56.07 ± 4.78 | |
5.0 | 39.33 ± 2.99 | 18.03 ± 2.30 | 19.46 ± 1.93 a | 62.40 ± 4.99 | |
8 weeks of age | |||||
Male | 0.0 | 34.35 ± 3.92 | 26.87 ± 2.99 | 15.32 ± 1.88 | 39.42 ± 4.61 |
0.1 | 31.76 ± 4.11 | 25.63 ± 3.74 | 16.71 ± 2.54 | 40.65 ± 5.62 | |
1.0 | 38.22 ± 3.83 | 23.68 ± 4.20 | 19.50 ± 1.93 | 42.98 ± 3.71 | |
5.0 | 32.42 ± 5.80 | 24.85 ± 3.52 | 21.79 ± 2.06 a | 46.93 ± 4.98 | |
Female | 0.0 | 36.16 ± 5.84 | 25.40 ± 3.58 | 19.78 ± 3.20 | 36.19 ± 3.36 |
0.1 | 35.68 ± 3.70 | 24.39 ± 4.24 | 20.04 ± 2.78 | 38.47 ± 5.44 | |
1.0 | 37.27 ± 4.48 | 23.88 ± 3.82 | 21.72 ± 3.43 | 42.80 ± 3.28 | |
5.0 | 34.89 ± 4.53 | 21.92 ± 4.03 | 25.69 ± 2.56 | 41.34 ± 4.60 |
© 2016 by the authors; 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 (http://creativecommons.org/licenses/by/4.0/).
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Zhong, S.-Q.; Chen, Z.-X.; Kong, M.-L.; Xie, Y.-Q.; Zhou, Y.; Qin, X.-D.; Paul, G.; Zeng, X.-W.; Dong, G.-H. Testosterone-Mediated Endocrine Function and TH1/TH2 Cytokine Balance after Prenatal Exposure to Perfluorooctane Sulfonate: By Sex Status. Int. J. Mol. Sci. 2016, 17, 1509. https://doi.org/10.3390/ijms17091509
Zhong S-Q, Chen Z-X, Kong M-L, Xie Y-Q, Zhou Y, Qin X-D, Paul G, Zeng X-W, Dong G-H. Testosterone-Mediated Endocrine Function and TH1/TH2 Cytokine Balance after Prenatal Exposure to Perfluorooctane Sulfonate: By Sex Status. International Journal of Molecular Sciences. 2016; 17(9):1509. https://doi.org/10.3390/ijms17091509
Chicago/Turabian StyleZhong, Shou-Qiang, Zan-Xiong Chen, Min-Li Kong, Yan-Qi Xie, Yang Zhou, Xiao-Di Qin, Gunther Paul, Xiao-Wen Zeng, and Guang-Hui Dong. 2016. "Testosterone-Mediated Endocrine Function and TH1/TH2 Cytokine Balance after Prenatal Exposure to Perfluorooctane Sulfonate: By Sex Status" International Journal of Molecular Sciences 17, no. 9: 1509. https://doi.org/10.3390/ijms17091509