The aquaglyceroporin AQP9 contributes to the sex-specific effects of in utero arsenic exposure on placental gene expressionReportar como inadecuado

The aquaglyceroporin AQP9 contributes to the sex-specific effects of in utero arsenic exposure on placental gene expression - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Environmental Health

, 16:59

Children’s Environmental Health


BackgroundSex-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.

MethodsUsing 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.

ResultsWe 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.

ConclusionsOur 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.

KeywordsArsenic AQP9 in utero Fetal placenta AbbreviationsEPA MCLEnvironmental Protection Agency’s Maximum Contaminant Level

IQRinterquartile range

NHBCSNew Hampshire Birth Cohort Study

U-Astotal maternal urinary arsenic concentration excluding arsenobetaine

Electronic supplementary materialThe online version of this article doi:10.1186-s12940-017-0267-8 contains supplementary material, which is available to authorized users.

Autor: Emily F. Winterbottom - Devin C. Koestler - Dennis Liang Fei - Eric Wika - Anthony J. Capobianco - Carmen J. Marsit - M


Documentos relacionados