{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T08:15:26Z","timestamp":1791101726653,"version":"4.1.0"},"reference-count":37,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":2808,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Bisphenol A (BPA), an endocrine disruptor, is a component of polycarbonate plastics, epoxy resins, and polystyrene. Several studies have reported potent in vivo effects, because BPA behaves as an estrogen agonist and\/or antagonist and as an androgen and thyroid hormone antagonist.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We investigated the effects of neonatal exposure to BPA on the reproductive axis in adult female Sprague-Dawley rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Female rats were injected subcutaneously, daily from postnatal day 1 (PND1) to PND10 with BPA in castor oil at 500 \u03bcg\/50 \u03bcL [BPA500; ~ 10\u22124 M, a dose higher than the lowest observed adverse effect level (LOAEL) of 50 mg\/kg], 50 \u03bcg\/50 \u03bcL (BPA50), or 5 \u03bcg\/50 \u03bcL (both BPA50 and BPA5 are doses lower than the LOAEL), or castor oil vehicle alone. In adults we studied a) the release of gonadotropin-releasing hormone (GnRH) from hypothalamic explants, b) serum sex hormone levels, and c) ovarian morphology, ovulation, and fertility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Neonatal exposure to BPA was associated with increased serum testosterone and estradiol levels, reduced progesterone in adulthood, and altered in vitro GnRH secretion. Animals exposed to BPA500 had altered ovarian morphology, showing a large number of cysts. Animals exposed to BPA50 had reduced fertility without changes in the number of oocytes on the morning of estrus, whereas animals exposed to BPA500 showed infertility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Exposure to high doses of BPA during the period of brain sexual differentiation altered the hypothalamic\u2013pituitary\u2013gonadal axis in female Sprague-Dawley rats. These results have the potential to link neonatal exposure to high doses of BPA in rats with the development of polycystic ovarian syndrome. Studies of doses and routes of administration more consistent with human exposures are needed to determine the relevance of these findings to human health.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1289\/ehp.0901257","type":"journal-article","created":{"date-parts":[[2010,4,22]],"date-time":"2010-04-22T16:14:04Z","timestamp":1271952844000},"page":"1217-1222","source":"Crossref","is-referenced-by-count":231,"title":["Neonatal Exposure to Bisphenol A and Reproductive and Endocrine Alterations Resembling the Polycystic Ovarian Syndrome in Adult Rats"],"prefix":"10.1021","volume":"118","author":[{"given":"Marina","family":"Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"Instituto de Biolog\u00eda y Medicina Experimental, Buenos Aires, Argentina"},{"name":"Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Bourguignon","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda y Medicina Experimental, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Lux-Lantos","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda y Medicina Experimental, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Libertun","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda y Medicina Experimental, Buenos Aires, Argentina"},{"name":"Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2010,4,22]]},"reference":[{"key":"2026080504144834900_micit1","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1095\/biolreprod.109.078261","article-title":"Neonatal bisphenol-A exposure alters rat reproductive development and ovarian morphology without impairing activation of gonadotropin releasing hormone neurons","volume":"81","author":"Adewale","year":"2009","journal-title":"Biol Reprod"},{"key":"2026080504144834900_micit2","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1289\/ehp.8451","article-title":"The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance","volume":"114","author":"Alonso-Magdalena","year":"2006","journal-title":"Environ Health Perspect"},{"key":"2026080504144834900_micit3","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1159\/000082527","article-title":"Effect of androgens on sexual differentiation of pituitary gamma-aminobutyric acid receptor subunit GABAB expression","volume":"80","author":"Bianchi","year":"2004","journal-title":"Neuroendocrinology"},{"key":"2026080504144834900_micit4","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1289\/ehp.0800265","article-title":"Exposure to bisphenol A and other phenols in neonatal intensive care unit premature infants","volume":"117","author":"Calafat","year":"2009","journal-title":"Environ Health Perspect"},{"key":"2026080504144834900_micit5","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/1477-7827-7-47","article-title":"The estrogen- injected female mouse: new insight into the etiology of PCOS","volume":"7","author":"Chapman","year":"2009","journal-title":"Reprod Biol Endocrinol"},{"key":"2026080504144834900_micit6","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.taap.2006.11.029","article-title":"Analysis of the interaction of phytoestrogens and synthetic chemicals: an in vitro\/in vivo comparison","volume":"218","author":"Charles","year":"2007","journal-title":"Toxicol Appl Pharmacol"},{"key":"2026080504144834900_micit7","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.fertnstert.2008.08.067","article-title":"Female reproductive disorders: the roles of endocrine-disrupting compounds and developmental timing","volume":"90","author":"Crain","year":"2008","journal-title":"Fertil Steril"},{"key":"2026080504144834900_micit8","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1210\/er.2009-0002","article-title":"Endocrine-disrupting chemicals: an Endocrine Society scientific statement","volume":"30","author":"Diamanti-Kandarakis","year":"2009","journal-title":"Endocr Rev"},{"key":"2026080504144834900_micit9","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1289\/ehp.9282","article-title":"Prenatal bisphenol A exposure induces preneoplastic lesions in the mammary gland in Wistar rats","volume":"115","author":"Durando","year":"2007","journal-title":"Environ Health Perspect"},{"key":"2026080504144834900_micit10","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1289\/ehp.0800073","article-title":"Predicting plasma concentrations of bisphenol A in children younger than 2 years of age after typical feeding schedules, using a physiologically based toxicokinetic model","volume":"117","author":"Edginton","year":"2009","journal-title":"Environ Health Perspect"},{"key":"2026080504144834900_micit11","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1289\/ehp.0800267","article-title":"Neonatal exposure to bisphenol A alters reproductive parameters and gonadotropin releasing hormone signaling in female rats","volume":"117","author":"Fern\u00e1ndez","year":"2009","journal-title":"Environ Health Perspect"},{"key":"2026080504144834900_micit12","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1007\/s00216-003-2380-5","article-title":"Bioassay-directed chemical analysis utilizing LC-MS: a tool for identifying estrogenic compounds in water samples?","volume":"378","author":"Heisterkamp","year":"2004","journal-title":"Anal Bioanal Chem"},{"key":"2026080504144834900_micit13","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1289\/ehp.11537","article-title":"Bisphenol A at environmentally relevant doses inhibits adiponectin release from human adipose tissue explants and adipocytes","volume":"116","author":"Hugo","year":"2008","journal-title":"Environ Health Perspect"},{"key":"2026080504144834900_micit14","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0890-6238(03)00002-9","article-title":"Changes in reproductive organs of female rats treated with bisphenol A during the neonatal period","volume":"17","author":"Kato","year":"2003","journal-title":"Reprod Toxicol"},{"issue":"suppl 4","key":"2026080504144834900_micit15","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1289\/ehp.96104s4715","article-title":"Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop","volume":"104","author":"Kavlock","year":"1996","journal-title":"Environ Health Perspect"},{"key":"2026080504144834900_micit16","doi-asserted-by":"crossref","first-page":"4512","DOI":"10.1210\/endo.141.12.7823","article-title":"Exposure of newborn male and female rats to environmental estrogens: delayed and sustained hyperprolactinemia and alterations in estrogen receptor expression","volume":"141","author":"Khurana","year":"2000","journal-title":"Endocrinology"},{"key":"2026080504144834900_micit17","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0303-7207(01)00611-6","article-title":"Hypothalamic dysfunction","volume":"183","author":"Marshall","year":"2001","journal-title":"Mol Cell Endocrinol"},{"key":"2026080504144834900_micit18","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1073\/pnas.89.5.1852","article-title":"Generation and synchronization of gonadotropin-releasing hormone (GnRH) pulses: intrinsic properties of the GT1-1 GnRH neuronal cell line","volume":"89","author":"Martinez de la Escalera","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026080504144834900_micit19","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1093\/toxsci\/kfi088","article-title":"Bisphenol A accelerates terminal differentiation of 3T3-L1 cells into adipocytes through the phosphatidylinositol 3-kinase pathway","volume":"84","author":"Masuno","year":"2005","journal-title":"Toxicol Sci"},{"key":"2026080504144834900_micit20","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1677\/JOE-07-0056","article-title":"Effect of prenatal exposure to the endocrine disruptor bisphenol A on mammary gland morphology and gene expression signature","volume":"196","author":"Moral","year":"2008","journal-title":"J Endocrinol"},{"key":"2026080504144834900_micit21","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1095\/biolreprod.104.034454","article-title":"Gonadotropin-releasing hormone antagonist antide inhibits apoptosis of preovulatory follicle cells in rat ovary","volume":"72","author":"Parborell","year":"2005","journal-title":"Biol Reprod"},{"key":"2026080504144834900_micit22","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ntt.2005.11.004","article-title":"Neonatal genistein or bisphenol-A exposure alters sexual differentiation of the AVPV","volume":"28","author":"Patisaul","year":"2006","journal-title":"Neurotoxicol Teratol"},{"key":"2026080504144834900_micit23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuro.2006.10.001","article-title":"Differential disruption of nuclear volume and neuronal phenotype in the preoptic area by neonatal exposure to genistein and bisphenol-A","volume":"28","author":"Patisaul","year":"2007","journal-title":"Neurotoxicology"},{"key":"2026080504144834900_micit24","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.anireprosci.2005.05.010","article-title":"The pituitary effects of GnRH","volume":"88","author":"Pawson","year":"2005","journal-title":"Anim Reprod Sci"},{"key":"2026080504144834900_micit25","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jsbmb.2008.02.006","article-title":"Dietary xenoestrogens differentially impair 3T3-L1 preadipocyte differentiation and persistently affect leptin synthesis","volume":"110","author":"Phrakonkham","year":"2008","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2026080504144834900_micit26","doi-asserted-by":"crossref","first-page":"3206","DOI":"10.1210\/en.2002-0198","article-title":"Bisphenol A induces both transient and permanent histofunctional alterations of the hypothalamic-pituitary-gonadal axis in prenatally exposed male rats","volume":"144","author":"Ramos","year":"2003","journal-title":"Endocrinology"},{"key":"2026080504144834900_micit27","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.reprotox.2007.06.004","article-title":"In vivo effects of bisphenol A in laboratory rodent studies","volume":"24","author":"Richter","year":"2007","journal-title":"Reprod Toxicol"},{"key":"2026080504144834900_micit28","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1289\/ehp.01109675","article-title":"Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrous cyclicity, and plasma LH levels","volume":"109","author":"Rubin","year":"2001","journal-title":"Environ Health Perspect"},{"key":"2026080504144834900_micit29","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.mce.2009.02.023","article-title":"Bisphenol A: perinatal exposure and body weight","volume":"304","author":"Rubin","year":"2009","journal-title":"Mol Cell Endocrinol"},{"key":"2026080504144834900_micit30","doi-asserted-by":"crossref","first-page":"E977","DOI":"10.1152\/ajpendo.00179.2007","article-title":"Both orexin receptors are expressed in rat ovaries and fluctuate with the estrous cycle: effects of orexin receptor antagonists on gonadotropins and ovulation","volume":"293","author":"Silveyra","year":"2007","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2026080504144834900_micit31","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1095\/biolreprod.107.063974","article-title":"Neonatal exposure to estradiol valerate programs ovarian sympathetic innervation and follicular development in the adult rat","volume":"78","author":"Sotomayor-Z\u00e1rate","year":"2008","journal-title":"Biol Reprod"},{"key":"2026080504144834900_micit32","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1507\/endocrj.51.165","article-title":"Positive relationship between androgen and the endocrine disruptor, bisphenol A, in normal women and women with ovarian dysfunction","volume":"51","author":"Takeuchi","year":"2004","journal-title":"Endocr J"},{"key":"2026080504144834900_micit33","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.reprotox.2008.01.001","article-title":"No effect of route of exposure (oral; subcutaneous injection) on plasma bisphenol A throughout 24h after administration in neonatal female mice","volume":"25","author":"Taylor","year":"2008","journal-title":"Reprod Toxicol"},{"key":"2026080504144834900_micit34","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.reprotox.2007.07.010","article-title":"Human exposure to bisphenol A (BPA)","volume":"24","author":"Vandenberg","year":"2007","journal-title":"Reprod Toxicol"},{"key":"2026080504144834900_micit35","doi-asserted-by":"crossref","first-page":"5848","DOI":"10.1210\/en.2008-0651","article-title":"Developmental exposure to bisphenol A impairs the uterine response to ovarian steroids in the adult","volume":"149","author":"Varayoud","year":"2008","journal-title":"Endocrinology"},{"key":"2026080504144834900_micit36","first-page":"E486","article-title":"Cluster analysis: a simple, versatile, and robust algorithm for endocrine pulse detection","volume":"250","author":"Veldhuis","year":"1986","journal-title":"Am J Physiol"},{"key":"2026080504144834900_micit37","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.reprotox.2007.05.010","article-title":"In vitro molecular mechanisms of bisphenol A action","volume":"24","author":"Wetherill","year":"2007","journal-title":"Reprod Toxicol"}],"container-title":["Environmental Health Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-pdf\/118\/9\/1217\/66401477\/ehp.0901257.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-pdf\/118\/9\/1217\/66401477\/ehp.0901257.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T13:47:49Z","timestamp":1786628869000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-lookup\/doi\/10.1289\/ehp.0901257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4,22]]},"references-count":37,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2010,4,22]]},"published-print":{"date-parts":[[2010,9,1]]}},"URL":"https:\/\/doi.org\/10.1289\/ehp.0901257","relation":{},"ISSN":["0091-6765","1552-9924"],"issn-type":[{"value":"0091-6765","type":"print"},{"value":"1552-9924","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,4,22]]}}}