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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EBisphenol A (BPA) is an industrial chemical used to make polycarbonate\u2014a hard, clear plastic used in many consumer products. Endocrine-disrupting effects of low BPA doses in the microgram range are a matter of controversy. However, this article reports that an injection of a very low dose (25 ng\/kg\/day) of BPA into neonatal rats delayed puberty, slowed down gonadotropin-releasing hormone secretion, and changed hypothalamic RNA expression.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Ediabetes \u0026amp; endocrinology clinical trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ehormone therapy\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EBisphenol A (BPA) is an industrial chemical used to make polycarbonate\u2014a hard, clear plastic used in many consumer products. It is also found in epoxy resins, which act as a protective lining inside some metal-based food and beverage cans. Endocrine-disrupting effects of low BPA doses in the microgram range are a matter of controversy. In a late-breaking presentation, Jean-Pierre Bourguignon, MD, PhD, University of Li\u00e8ge, Li\u00e8ge, Belgium, reported that injection of a very low dose (25 ng\/kg\/day) of BPA into neonatal rats delayed puberty, slowed down gonadotropin-releasing hormone (GnRH) secretion, and changed hypothalamic RNA expression. Opposing effects, including early puberty, were observed with a high dose (5 mg\/kg\/day).\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EA related study reported on the effects of neonatal exposure to diethylstilbestrol (DES) on pubertal timing in female rats, showing that age at vaginal opening (VO) was advanced after exposure to 10 \u00b5g\/kg\/day of DES and delayed after 1 \u00b5g\/kg\/day, given subcutaneously [Franssen D et al. \u003Cem\u003EReprod Toxicol\u003C\/em\u003E 2014]. There were also consistent changes in maturation of pulsatile GnRH secretion.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EIn the current study, newborn female rats were exposed to vehicle (corn oil) or BPA, injected subcutaneously from postnatal day (PND) 1 to 5 or from PND 1 to 15. VO and estrous cyclicity were followed. The GnRH interpulse was studied ex vivo with hypothalamic explants obtained at PND 15, 20, or 25. Gene expression in the retrochiasmatic hypothalamus was assessed by whole-exome RNA sequencing on PND 20 (3 samples per condition).\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EThe age at VO after neonatal exposure to 25 ng\/kg\/day of BPA for 15 days was 35.3 \u00b1 0.7 days, compared with 32.1 \u00b1 0.6 days at 5 mg\/kg\/day. In animals receiving vehicle (control), VO was 33.5 \u00b1 0.5 days. Thus, the high dose advanced, and the low dose delayed, the age at VO compared with the control (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). The difference in pubertal timing between the 2 doses was significant (p \u0026lt; .05).\u003C\/p\u003E\n         \u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/9\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Median Age at Vaginal Opening After High and Low Doses of BPA\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-645308168\u0022 data-figure-caption=\u0022Median Age at Vaginal Opening After High and Low Doses of BPA\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/9\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/9\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/9\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16452\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-6\u0022 class=\u0022first-child\u0022\u003EMedian Age at Vaginal Opening After High and Low Doses of BPA\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EBPA=bisphenol A.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-7\u0022\u003ELate VO came after exposure to 25 ng\/kg\/day of BPA and was preceded at PND 20 by a significant increase in GnRH interpulse interval (52.5 \u00b1 0.8 min vs 44.6 \u00b1 0.7 min in controls). Early VO after exposure to 5 mg\/kg\/day, however, was preceded by a significant decrease in GnRH interpulse interval (40.3 \u00b1 0.1 min vs 42.8 \u00b1 0.4 min; \u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E). After BPA exposure from PND 1 to 5, comparable dose-related changes in GnRH secretion were observed.\u003C\/p\u003E\n         \u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/9\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022GnRH Interpulse Interval After Exposure to High and Low Doses of BPA\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-645308168\u0022 data-figure-caption=\u0022GnRH Interpulse Interval After Exposure to High and Low Doses of BPA\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/9\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/9\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/9\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16453\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003EGnRH Interpulse Interval After Exposure to High and Low Doses of BPA\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EBPA=bisphenol A; GnRH=gonadotropin-releasing hormone.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-9\u0022\u003ERNA expression of 10 genes showed significant opposing changes in the high- versus low-dose groups at PND 20. The dose of 25 ng\/kg affected expression of 14 genes, while 5 mg\/kg modified the expression of 472 genes versus controls. A significant difference in levels of RNA expression was observed for 1407 genes when the 2 BPA dose conditions were compared.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003ENeonatal exposure to a very low dose of BPA delayed pubertal onset, slowed GnRH secretion, and changed hypothalamic RNA expression. Changed hypothalamic RNA expression confirmed the neuroendocrine effects of the 2 BPA doses, with opposing changes of similar genes in relation to BPA dose and with alteration of distinct genes by each dose.\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EWhile these data add to the large body of evidence in animal models concerning the effects of BPA on the female reproductive tract [Caserta et al. \u003Cem\u003EReprod Biol Endocrinol\u003C\/em\u003E 2014], the influence of BPA on the pathogenesis of premature puberty in girls has not been confirmed. Some have found a correlation between pubertal stages and BPA serum or urinary levels [Qiao et al. \u003Cem\u003EWei Sheng Yan Jiu\u003C\/em\u003E 2010; Durmaz et al. \u003Cem\u003EJ Clin Res Pediatr Endocrinol\u003C\/em\u003E 2014], while others have found conflicting data [Wolff et al. \u003Cem\u003EEnviron Res\u003C\/em\u003E 2008; Yum et al. \u003Cem\u003EJ Environ Sci Health A Tox Hazard Subst Environ Eng\u003C\/em\u003E 2013] perhaps due to confounding variables, such as body mass index and race [Wolff et al. \u003Cem\u003EEnviron Health Perspect\u003C\/em\u003E 2007]. More studies need to be conducted in humans.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/20\/9.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzoy41\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzoy41\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}