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It has been quite established that acute alcohol exposure can dramatically affect astrocyte function. Because the effects of early alcohol exposure on cell physiology can persist into adulthood, we tested the hypothesis that ethanol exposure in ferrets during a period equivalent to the last months of human gestation leads to persistent changes in astrocyte secretome <jats:italic>in\u00a0vitro<\/jats:italic>. Animals were treated with ethanol (3.5\u00a0g\/kg) or saline between postnatal day (P)10\u201330. At P31, astrocyte cultures were made and cells were submitted to stable isotope labeling by amino acids. Twenty\u2010four hour conditioned media of cells obtained from ethanol\u2010 or saline\u2010treated animals (<jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">SAL<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content>) were collected and analyzed by quantitative mass spectrometry in tandem with liquid chromatography. Here, we show that 65 out of 280 quantifiable proteins displayed significant differences comparing <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content> to <jats:styled-content style=\"fixed-case\">SAL<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content>. Among the 59 proteins that were found to be reduced in <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content> we observed components of the extracellular matrix such as laminin subunits \u03b12, \u03b14, \u03b21, \u03b22, and \u03b31 and the proteoglycans biglycan, heparan sulfate proteoglycan 2, and lumican. Proteins with trophic function such as insulin\u2010like growth factor binding protein 4, pigment epithelium\u2010derived factor, and clusterin as well as proteins involved on modulation of proteolysis such as metalloproteinase inhibitor 1 and plasminogen activator inhibitor\u20101 were also reduced. In contrast, pro\u2010synaptogeneic proteins like thrombospondin\u20101, hevin as well as the modulator of extracelular matrix expression, angiotensinogen, were found increased in <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content>. The analysis of interactome maps through ingenuity pathway analysis demonstrated that the amyloid beta A4 protein precursor, which was found reduced in <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content>, was previously shown to interact with ten other proteins that exhibited significant changes in the <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content>. Taken together our results strongly suggest that early exposure to teratogens such as alcohol may lead to an enduring change in astrocyte secretome.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13542-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>Despite efforts in prevention, fetal alcohol spectrum disorders are a major cause of mental disabilities. Here, we show that developmental exposure to alcohol lead to a persistent change in the pattern of proteins secreted (secretome) by astrocytes. This study is also the first mass spectrometry\u2010based assessment of the astrocyte secretome in a gyrencephalic animal.\n<\/jats:p><jats:p><jats:bold>Cover Image<\/jats:bold> for this issue: doi: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1111\/jnc.13320\">10.1111\/jnc.13320<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13542","type":"journal-article","created":{"date-parts":[[2016,1,23]],"date-time":"2016-01-23T07:02:21Z","timestamp":1453532541000},"page":"730-743","source":"Crossref","is-referenced-by-count":28,"title":["Developmental alcohol exposure leads to a persistent change on astrocyte secretome"],"prefix":"10.1111","volume":"137","author":[{"given":"Pablo","family":"Trindade","sequence":"first","affiliation":[{"name":"Department of Pediatrics School of Medicine University of Maryland Baltimore Maryland 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