The aquaglyceroporin AQP9 contributes to the sex-specific effects of in utero arsenic exposure on placental gene expression
Abstract Background Sex-specific factors play a major role in human health and disease, including responses to environmental stresses such as toxicant exposure. Increasing evidence suggests that such sex differences also exist during fetal development. In a previous report using the resources of the...
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| Format: | Article |
| Language: | English |
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BMC
2017-06-01
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| Series: | Environmental Health |
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| Online Access: | http://link.springer.com/article/10.1186/s12940-017-0267-8 |
| _version_ | 1828400597910421504 |
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| author | Emily F. Winterbottom Devin C. Koestler Dennis Liang Fei Eric Wika Anthony J. Capobianco Carmen J. Marsit Margaret R. Karagas David J. Robbins |
| author_facet | Emily F. Winterbottom Devin C. Koestler Dennis Liang Fei Eric Wika Anthony J. Capobianco Carmen J. Marsit Margaret R. Karagas David J. Robbins |
| author_sort | Emily F. Winterbottom |
| collection | DOAJ |
| description | Abstract Background Sex-specific factors play a major role in human health and disease, including responses to environmental stresses such as toxicant exposure. Increasing evidence suggests that such sex differences also exist during fetal development. In a previous report using the resources of the New Hampshire Birth Cohort Study (NHBCS), we found that low-to-moderate in utero exposure to arsenic, a highly toxic and widespread pollutant, was associated with altered expression of several key developmental genes in the fetal portion of the placenta. These associations were sex-dependent, suggesting that in utero arsenic exposure differentially impacts male and female fetuses. In the present study, we investigated the molecular basis for these sex-specific responses to arsenic. Methods Using NanoString technology, we further analyzed the fetal placenta samples from the NHBCS for the expression of genes encoding arsenic transporters and metabolic enzymes. Multivariable linear regression analysis was used to examine their relationship with arsenic exposure and with key developmental genes, after stratification by fetal sex. Results We found that maternal arsenic exposure was strongly associated with expression of the AQP9 gene, encoding an aquaglyceroporin transporter, in female but not male fetal placenta. Moreover, AQP9 expression associated with that of a subset of female-specific arsenic-responsive genes. Conclusions Our results suggest that AQP9 is upregulated in response to arsenic exposure in female, but not male, fetal placenta. Based on these results and prior studies, increased AQP9 expression may lead to increased arsenic transport in the female fetal placenta, which in turn may alter the expression patterns of key developmental genes that we have previously shown to be associated with arsenic exposure. Thus, this study suggests that AQP9 may play a role in the sex-specific effects of in utero arsenic exposure. |
| first_indexed | 2024-12-10T09:34:36Z |
| format | Article |
| id | doaj.art-2fd35b02983a4639922d99b0ae8e2afc |
| institution | Directory Open Access Journal |
| issn | 1476-069X |
| language | English |
| last_indexed | 2024-12-10T09:34:36Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Environmental Health |
| spelling | doaj.art-2fd35b02983a4639922d99b0ae8e2afc2022-12-22T01:54:13ZengBMCEnvironmental Health1476-069X2017-06-011611910.1186/s12940-017-0267-8The aquaglyceroporin AQP9 contributes to the sex-specific effects of in utero arsenic exposure on placental gene expressionEmily F. Winterbottom0Devin C. Koestler1Dennis Liang Fei2Eric Wika3Anthony J. Capobianco4Carmen J. Marsit5Margaret R. Karagas6David J. Robbins7Molecular Oncology Program, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of MedicineDepartment of Biostatistics, University of Kansas Medical CenterMolecular Oncology Program, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of MedicineDepartment of Biostatistics, University of Kansas Medical CenterMolecular Oncology Program, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of MedicineDepartment of Environmental Health, Rollins School of Public Health at Emory UniversityDepartment of Epidemiology, Geisel School of Medicine at DartmouthMolecular Oncology Program, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of MedicineAbstract Background Sex-specific factors play a major role in human health and disease, including responses to environmental stresses such as toxicant exposure. Increasing evidence suggests that such sex differences also exist during fetal development. In a previous report using the resources of the New Hampshire Birth Cohort Study (NHBCS), we found that low-to-moderate in utero exposure to arsenic, a highly toxic and widespread pollutant, was associated with altered expression of several key developmental genes in the fetal portion of the placenta. These associations were sex-dependent, suggesting that in utero arsenic exposure differentially impacts male and female fetuses. In the present study, we investigated the molecular basis for these sex-specific responses to arsenic. Methods Using NanoString technology, we further analyzed the fetal placenta samples from the NHBCS for the expression of genes encoding arsenic transporters and metabolic enzymes. Multivariable linear regression analysis was used to examine their relationship with arsenic exposure and with key developmental genes, after stratification by fetal sex. Results We found that maternal arsenic exposure was strongly associated with expression of the AQP9 gene, encoding an aquaglyceroporin transporter, in female but not male fetal placenta. Moreover, AQP9 expression associated with that of a subset of female-specific arsenic-responsive genes. Conclusions Our results suggest that AQP9 is upregulated in response to arsenic exposure in female, but not male, fetal placenta. Based on these results and prior studies, increased AQP9 expression may lead to increased arsenic transport in the female fetal placenta, which in turn may alter the expression patterns of key developmental genes that we have previously shown to be associated with arsenic exposure. Thus, this study suggests that AQP9 may play a role in the sex-specific effects of in utero arsenic exposure.http://link.springer.com/article/10.1186/s12940-017-0267-8ArsenicAQP9in uteroFetal placenta |
| spellingShingle | Emily F. Winterbottom Devin C. Koestler Dennis Liang Fei Eric Wika Anthony J. Capobianco Carmen J. Marsit Margaret R. Karagas David J. Robbins The aquaglyceroporin AQP9 contributes to the sex-specific effects of in utero arsenic exposure on placental gene expression Environmental Health Arsenic AQP9 in utero Fetal placenta |
| title | The aquaglyceroporin AQP9 contributes to the sex-specific effects of in utero arsenic exposure on placental gene expression |
| title_full | The aquaglyceroporin AQP9 contributes to the sex-specific effects of in utero arsenic exposure on placental gene expression |
| title_fullStr | The aquaglyceroporin AQP9 contributes to the sex-specific effects of in utero arsenic exposure on placental gene expression |
| title_full_unstemmed | The aquaglyceroporin AQP9 contributes to the sex-specific effects of in utero arsenic exposure on placental gene expression |
| title_short | The aquaglyceroporin AQP9 contributes to the sex-specific effects of in utero arsenic exposure on placental gene expression |
| title_sort | aquaglyceroporin aqp9 contributes to the sex specific effects of in utero arsenic exposure on placental gene expression |
| topic | Arsenic AQP9 in utero Fetal placenta |
| url | http://link.springer.com/article/10.1186/s12940-017-0267-8 |
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