Effects of Cyclosporine A on the Development of Metanephros in the Pregnant BALB/c Mice
Background: Cyclosporine A (CsA) is a commonly used clinical immunosuppressant. However, CsA exposure in rabbits during the gestation period was shown to cause a postnatal decrease in the number of nephrons, with the effects remaining unknown. In this study, we aimed to explore the effects of CsA on...
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Wolters Kluwer
2017-01-01
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| Series: | Chinese Medical Journal |
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| Online Access: | http://www.cmj.org/article.asp?issn=0366-6999;year=2017;volume=130;issue=18;spage=2156;epage=2162;aulast=Liao |
| _version_ | 1811326908736995328 |
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| author | Yu-Jie Liao Rong-Shuang Huang Wei-Jing Lai Fang Liu Liang Ma Yuan-Sheng Xie Stephen Salerno Yi Li Ping Fu |
| author_facet | Yu-Jie Liao Rong-Shuang Huang Wei-Jing Lai Fang Liu Liang Ma Yuan-Sheng Xie Stephen Salerno Yi Li Ping Fu |
| author_sort | Yu-Jie Liao |
| collection | DOAJ |
| description | Background: Cyclosporine A (CsA) is a commonly used clinical immunosuppressant. However, CsA exposure in rabbits during the gestation period was shown to cause a postnatal decrease in the number of nephrons, with the effects remaining unknown. In this study, we aimed to explore the effects of CsA on metanephros development in the pregnant BALB/c mice.
Methods: Pregnant mice were randomly divided into two groups, and CsA (10 mg·kg−1·d−1) was subcutaneously injected from gestation day 10.5 to day 16.5 in the CsA group, whereas a comparable volume of normal saline was given to the control group. All of the mice were sacrificed on gestation day 17.5 and serum CsA concentration was measured. The fetuses were removed and weighed, and their kidneys were prepared for histological assessment and polymerase chain reaction assay. In an in vitro experiment, embryo kidneys of fetal mice on gestation day 12.5 were used, and CsA (10 μmol/L) was added in the culture of the CsA group. The growth pattern of the ureteric bud and nephrons was assessed by lectin staining.
Results: No significant differences in the weight of embryo (4.54 ± 1.22 vs. 3.26 ± 1.09 mg) were observed between the CsA and control groups, the thickness of the cortical (510.0 ± 30.3 vs. 350.0 ± 29.7 μm, P < 0.05) and nephrogenic zone (272.5 ± 17.2 vs. 173.3 ± 24.0 μm, P < 0.05), and the number of glomeruli (36.5 ± 0.7 vs. 27.5 ± 2.1, P < 0.05) were reduced in the CsA group when compared to the control group. The cell proliferation of Ki-67 positive index between control and CsA group (307.0 ± 20.0 vs. 219.0 ± 25.0, P < 0.05) in the nephrogenic zone was decreased with the increase of apoptotic cells (17.0 ± 2.0 vs. 159.0 ± 33.0, P < 0.05). The mRNA expression of WT-1, Pax2, and Pax8 was downregulated by CsA treatment. As for the in vitro CsA group, the branch number of the ureteric bud was decreased in the CsA-treated group with the nephrons missing in contrast to control after the incubation for 24 h and 72 h (all P < 0.0001).
Conclusion: Treatment of CsA suppressed metanephros development in the pregnant mice; however, the potential action of mechanism needs to be further investigated. |
| first_indexed | 2024-04-13T14:56:35Z |
| format | Article |
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| issn | 0366-6999 |
| language | English |
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| publishDate | 2017-01-01 |
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| spelling | doaj.art-d176ba1aa5e2473dabe96b43bef243ed2022-12-22T02:42:25ZengWolters KluwerChinese Medical Journal0366-69992017-01-01130182156216210.4103/0366-6999.213971Effects of Cyclosporine A on the Development of Metanephros in the Pregnant BALB/c MiceYu-Jie LiaoRong-Shuang HuangWei-Jing LaiFang LiuLiang MaYuan-Sheng XieStephen SalernoYi LiPing FuBackground: Cyclosporine A (CsA) is a commonly used clinical immunosuppressant. However, CsA exposure in rabbits during the gestation period was shown to cause a postnatal decrease in the number of nephrons, with the effects remaining unknown. In this study, we aimed to explore the effects of CsA on metanephros development in the pregnant BALB/c mice. Methods: Pregnant mice were randomly divided into two groups, and CsA (10 mg·kg−1·d−1) was subcutaneously injected from gestation day 10.5 to day 16.5 in the CsA group, whereas a comparable volume of normal saline was given to the control group. All of the mice were sacrificed on gestation day 17.5 and serum CsA concentration was measured. The fetuses were removed and weighed, and their kidneys were prepared for histological assessment and polymerase chain reaction assay. In an in vitro experiment, embryo kidneys of fetal mice on gestation day 12.5 were used, and CsA (10 μmol/L) was added in the culture of the CsA group. The growth pattern of the ureteric bud and nephrons was assessed by lectin staining. Results: No significant differences in the weight of embryo (4.54 ± 1.22 vs. 3.26 ± 1.09 mg) were observed between the CsA and control groups, the thickness of the cortical (510.0 ± 30.3 vs. 350.0 ± 29.7 μm, P < 0.05) and nephrogenic zone (272.5 ± 17.2 vs. 173.3 ± 24.0 μm, P < 0.05), and the number of glomeruli (36.5 ± 0.7 vs. 27.5 ± 2.1, P < 0.05) were reduced in the CsA group when compared to the control group. The cell proliferation of Ki-67 positive index between control and CsA group (307.0 ± 20.0 vs. 219.0 ± 25.0, P < 0.05) in the nephrogenic zone was decreased with the increase of apoptotic cells (17.0 ± 2.0 vs. 159.0 ± 33.0, P < 0.05). The mRNA expression of WT-1, Pax2, and Pax8 was downregulated by CsA treatment. As for the in vitro CsA group, the branch number of the ureteric bud was decreased in the CsA-treated group with the nephrons missing in contrast to control after the incubation for 24 h and 72 h (all P < 0.0001). Conclusion: Treatment of CsA suppressed metanephros development in the pregnant mice; however, the potential action of mechanism needs to be further investigated.http://www.cmj.org/article.asp?issn=0366-6999;year=2017;volume=130;issue=18;spage=2156;epage=2162;aulast=LiaoApoptosis; Cyclosporine A; Metanephros; Nephron; Ureteric Bud |
| spellingShingle | Yu-Jie Liao Rong-Shuang Huang Wei-Jing Lai Fang Liu Liang Ma Yuan-Sheng Xie Stephen Salerno Yi Li Ping Fu Effects of Cyclosporine A on the Development of Metanephros in the Pregnant BALB/c Mice Chinese Medical Journal Apoptosis; Cyclosporine A; Metanephros; Nephron; Ureteric Bud |
| title | Effects of Cyclosporine A on the Development of Metanephros in the Pregnant BALB/c Mice |
| title_full | Effects of Cyclosporine A on the Development of Metanephros in the Pregnant BALB/c Mice |
| title_fullStr | Effects of Cyclosporine A on the Development of Metanephros in the Pregnant BALB/c Mice |
| title_full_unstemmed | Effects of Cyclosporine A on the Development of Metanephros in the Pregnant BALB/c Mice |
| title_short | Effects of Cyclosporine A on the Development of Metanephros in the Pregnant BALB/c Mice |
| title_sort | effects of cyclosporine a on the development of metanephros in the pregnant balb c mice |
| topic | Apoptosis; Cyclosporine A; Metanephros; Nephron; Ureteric Bud |
| url | http://www.cmj.org/article.asp?issn=0366-6999;year=2017;volume=130;issue=18;spage=2156;epage=2162;aulast=Liao |
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