{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T10:02:30Z","timestamp":1790330550986,"version":"4.1.0"},"reference-count":31,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T00:00:00Z","timestamp":1603238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Merck Serono","award":["na"],"award-info":[{"award-number":["na"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Background: folliculogenesis is a strictly regulated process that may be affected by endocrine disrupting chemicals (EDCs) through sometimes not so clear molecular mechanisms. Methods: we conducted a multicentric observational study involving six fertility centers across Italy, prospectively recruiting 122 women attending a fertility treatment. Recruited women had age \u226442 years, and normal ovarian reserve. Blood and follicular fluid samples were taken for EDCs measurement using liquid chromatography tandem mass spectrometry and each woman completed an epidemiological questionnaire. Results: The main EDCs found were monobutyl phthalate (MBP) (median blood: 8.96 ng\/mL, follicular fluid 6.43 ng\/mL), monoethylhexyl phthalate (MEHP) (median blood: 9.16 ng\/mL, follicular fluid 7.68 ng\/mL) and bisphenol A (BPA) (median blood: 1.89 ng\/mL, follicular fluid 1.86 ng\/mL). We found that serum MBP concentration was significantly associated with the considered area (p &lt; 0.001, adj. mean: 7.61 ng\/mL, 14.40 ng\/mL, 13.56 ng\/mL; Area 1: Milan\u2013Turin, Area 2: Rome\u2013Naples; Area 3: Catania\u2013Bari, respectively) but negatively with home plastic food packaging (p = 0.004). Follicular MBP was associated with irregular cycles (p = 0.019). No association was detected between EDCs and eating habits and other clinical and epidemiological features. Conclusions: This study represents the first Italian biomonitoring of plastic EDCs in follicular fluid, laying the basis for future prospective evaluation on oocyte quality before assisted reproduction techniques (ART).<\/jats:p>","DOI":"10.3390\/toxics8040091","type":"journal-article","created":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T02:01:42Z","timestamp":1603418502000},"page":"91","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Phthalates and Bisphenol A: Presence in Blood Serum and Follicular Fluid of Italian Women Undergoing Assisted Reproduction Techniques"],"prefix":"10.3390","volume":"8","author":[{"given":"Donatella","family":"Paoli","sequence":"first","affiliation":[{"name":"Laboratory of Seminology\u2014Sperm Bank \u201cLoredana Gandini\u201d, Department of Experimental Medicine, \u201cSapienza\u201d, University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6042-6474","authenticated-orcid":false,"given":"Francesco","family":"Pallotti","sequence":"additional","affiliation":[{"name":"Laboratory of Seminology\u2014Sperm Bank \u201cLoredana Gandini\u201d, Department of Experimental Medicine, \u201cSapienza\u201d, University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Pia","family":"Dima","sequence":"additional","affiliation":[{"name":"Laboratory of Seminology\u2014Sperm Bank \u201cLoredana Gandini\u201d, Department of Experimental Medicine, \u201cSapienza\u201d, University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Albani","sequence":"additional","affiliation":[{"name":"Humanitas Fertility Center, Department of Gynecology, Division of Gynecology and Reproductive Medicine, Humanitas Clinical and Research Hospital\u2014IRCCS, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Alviggi","sequence":"additional","affiliation":[{"name":"Istituto per l\u2019Endocrinologia e l\u2019Oncologia sperimentale Consiglio Nazionale delle Ricerche, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Causio","sequence":"additional","affiliation":[{"name":"Medical Centre San Luca, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5335-031X","authenticated-orcid":false,"given":"Carola Conca","family":"Dioguardi","sequence":"additional","affiliation":[{"name":"Humanitas Fertility Center, Department of Gynecology, Division of Gynecology and Reproductive Medicine, Humanitas Clinical and Research Hospital\u2014IRCCS, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5676-0055","authenticated-orcid":false,"given":"Alessandro","family":"Conforti","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples Federico II, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Ciriminna","sequence":"additional","affiliation":[{"name":"Centro AMBRA-Palermo, 90138 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Fabozzi","sequence":"additional","affiliation":[{"name":"Clinica Valle Giulia, G.en.e.r.a. Centers for Reproductive Medicine, 00197 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Giuffrida","sequence":"additional","affiliation":[{"name":"CRA, Assisted Reproductive Center, 95128 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Gualtieri","sequence":"additional","affiliation":[{"name":"Department Biology, University of Naples Federico II, University of Naples Federico II, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3624-6961","authenticated-orcid":false,"given":"Maria Giulia","family":"Minasi","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, European Hospital-Rome, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Ochetti","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Gynecology and Obstetrics 1 Physiopathology of Reproduction and IVF Unit, S. Anna Hospital, University of Torino, 10124 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4247-1970","authenticated-orcid":false,"given":"Valerio","family":"Pisaturo","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Department, International Evangelical Hospital, 16122 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Racca","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Gynecology and Obstetrics 1 Physiopathology of Reproduction and IVF Unit, S. Anna Hospital, University of Torino, 10124 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rienzi","sequence":"additional","affiliation":[{"name":"Clinica Valle Giulia, G.en.e.r.a. Centers for Reproductive Medicine, 00197 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Sarcina","sequence":"additional","affiliation":[{"name":"Medical Centre San Luca, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catello","family":"Scarica","sequence":"additional","affiliation":[{"name":"Casa di cura Villa Salaria in partnership with Institut Marques, 00139 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Tomasi","sequence":"additional","affiliation":[{"name":"CRA, Assisted Reproductive Center, 95128 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Verlengia","sequence":"additional","affiliation":[{"name":"UOSD Centro PMA Sant\u2019 Anna\u2014ASL Roma 1, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Villeggia","sequence":"additional","affiliation":[{"name":"UOSD Centro PMA Sant\u2019 Anna\u2014ASL Roma 1, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Zullo","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Gynecology and Obstetrics 1 Physiopathology of Reproduction and IVF Unit, S. Anna Hospital, University of Torino, 10124 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Lenzi","sequence":"additional","affiliation":[{"name":"Laboratory of Seminology\u2014Sperm Bank \u201cLoredana Gandini\u201d, Department of Experimental Medicine, \u201cSapienza\u201d, University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5296-8126","authenticated-orcid":false,"given":"Francesco","family":"Botr\u00e8","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, \u201cSapienza\u201d, University of Rome, 00153 Rome, Italy"},{"name":"Laboratorio Antidoping, Federazione Medico Sportiva Italiana, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"De Santis","sequence":"additional","affiliation":[{"name":"IVF Unit, San Raffaele Scientific Institute Deparment Ob\/Gyn, Vita-Salute University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.etap.2017.02.024","article-title":"Human exposure to endocrine disrupting chemicals: Effects on the male and female reproductive systems","volume":"51","author":"Sifakis","year":"2017","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1093\/toxsci\/kfz047","article-title":"Ovarian Metabolism of an Environmentally Relevant Phthalate Mixture","volume":"169","author":"Warner","year":"2019","journal-title":"Toxicol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.etap.2013.03.014","article-title":"Phthalates: European regulation, chemistry, pharmacokinetic and related toxicity","volume":"36","author":"Ventrice","year":"2013","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.fertnstert.2016.06.043","article-title":"Environmental exposure to endocrine-disrupting chemicals and miscarriage","volume":"106","author":"Krieg","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.ijheh.2007.07.011","article-title":"Phthalates: Toxicology and exposure","volume":"210","author":"Heudorf","year":"2007","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1289\/ehp.5658","article-title":"Mechanisms of phthalate ester toxicity in the female reproductive system","volume":"111","author":"Davis","year":"2003","journal-title":"Environ. Health Perspect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.envint.2015.06.008","article-title":"Pharmacokinetics of bisphenol A in humans following a single oral administration","volume":"83","author":"Thayer","year":"2015","journal-title":"Environ. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1095\/biolreprod.115.130336","article-title":"Effects of Endocrine-Disrupting Chemicals on the Ovary1","volume":"93","author":"Patel","year":"2015","journal-title":"Biol. Reprod."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Pallotti, F., Pelloni, M., Gianfrilli, D., Lenzi, A., Lombardo, F., and Paoli, D. (2020). Mechanisms of Testicular Disruption from Exposure to Bisphenol A and Phtalates. J. Clin. Med., 9.","DOI":"10.3390\/jcm9020471"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6278","DOI":"10.1177\/0300060519876467","article-title":"The effects of di(2-ethylhexyl) phthalate exposure in women with polycystic ovary syndrome undergoing In Vitro fertilization","volume":"47","author":"Jin","year":"2019","journal-title":"J. Int. Med. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"109884","DOI":"10.1016\/j.ecoenv.2019.109884","article-title":"The associations of urinary phthalate metabolites with the intermediate and pregnancy outcomes of women receiving IVF\/ICSI treatments: A prospective single-center study","volume":"188","author":"Deng","year":"2019","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1530\/REP-11-0136","article-title":"Endocrine-disrupting chemicals in ovarian function: Effects on steroidogenesis, metabolism and nuclear receptor signaling","volume":"142","author":"Craig","year":"2011","journal-title":"Reproduction"},{"key":"ref_13","first-page":"3375","article-title":"The correlation between exposure to BPA and the decrease of the ovarian reserve","volume":"11","author":"Cao","year":"2018","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.reprotox.2020.07.009","article-title":"Urinary bisphenol A concentrations and in vitro fertilization outcomes among women from a fertility clinic","volume":"96","author":"Radwan","year":"2020","journal-title":"Reprod. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1093\/humupd\/dmw027","article-title":"Interactions between androgens, FSH, anti-M\u00fcllerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary","volume":"22","author":"Dewailly","year":"2016","journal-title":"Hum. Reprod. Updat."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.mce.2011.10.021","article-title":"Impact of endocrine-disrupting compounds (EDCs) on female reproductive health","volume":"355","author":"Fowler","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1210\/er.2015-1010","article-title":"EDC-2: The Endocrine Society\u2019s Second Scientific Statement on Endocrine-Disrupting Chemicals","volume":"36","author":"Gore","year":"2015","journal-title":"Endocr. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3389\/fendo.2015.00008","article-title":"The Effects of Phthalates on the Ovary","volume":"6","author":"Hannon","year":"2015","journal-title":"Front. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.taap.2009.05.022","article-title":"Effect of mono-(2-ethylhexyl) phthalate on steroid production of human granulosa cells","volume":"239","author":"Reinsberg","year":"2009","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1093\/molehr\/gau045","article-title":"Effects of the environmental contaminants DEHP and TCDD on estradiol synthesis and aryl hydrocarbon receptor and peroxisome proliferator-activated receptor signalling in the human granulosa cell line KGN","volume":"20","author":"Ernst","year":"2014","journal-title":"Mol. Hum. Reprod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1095\/biolreprod.110.087015","article-title":"The Ability of the Aryl Hydrocarbon Receptor to Regulate Ovarian Follicle Growth and Estradiol Biosynthesis in Mice Depends on Stage of Sexual Maturity1","volume":"83","author":"Dehlinger","year":"2010","journal-title":"Biol. Reprod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.chemosphere.2019.04.174","article-title":"BPA activates EGFR and ERK1\/2 through PPAR\u03b3 to increase expression of steroidogenic acute regulatory protein in human cumulus granulosa cells","volume":"229","author":"Nenadov","year":"2019","journal-title":"Chemosphere"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.1093\/humrep\/17.11.2839","article-title":"Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure","volume":"17","author":"Ikezuki","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1007\/s10815-012-9775-1","article-title":"Phthalates and bisphenol do not accumulate in human follicular fluid","volume":"29","author":"Krotz","year":"2012","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.reprotox.2016.04.005","article-title":"Follicular fluid and urinary concentrations of phthalate metabolites among infertile women and associations with in vitro fertilization parameters","volume":"61","author":"Du","year":"2016","journal-title":"Reprod. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1289\/ehp.1510803","article-title":"Recent Fast Food Consumption and Bisphenol A and Phthalates Exposures among the U.S. Population in NHANES, 2003\u20132010","volume":"124","author":"Zota","year":"2016","journal-title":"Environ. Health Perspect."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Liao, C., Liu, W., Zhang, J., Shi, W., Wang, X., Cai, J., Zou, Z., Lu, R., Sun, C., and Wang, H. (2018). Associations of urinary phthalate metabolites with residential characteristics, lifestyles, and dietary habits among young children in Shanghai, China. Sci. Total Environ., 1288\u20131297.","DOI":"10.1016\/j.scitotenv.2017.10.189"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"105103","DOI":"10.1016\/j.envint.2019.105103","article-title":"The Norwegian biomonitoring study from the EU project EuroMix: Levels of phenols and phthalates in 24-h urine samples and exposure sources from food and personal care products","volume":"132","author":"Andreassen","year":"2019","journal-title":"Environ. Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4428","DOI":"10.1016\/j.fct.2012.09.004","article-title":"Effect of cooking at home on the levels of eight phthalates in foods","volume":"50","author":"Fierens","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7337","DOI":"10.1021\/acs.est.9b02123","article-title":"Characterizing Airborne Phthalate Concentrations and Dynamics in a Normally Occupied Residence","volume":"53","author":"Lunderberg","year":"2019","journal-title":"Environ. Sci. Technol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ijheh.2019.10.002","article-title":"Changes in urinary excretion of phthalates, phthalate substitutes, bisphenols and other polychlorinated and phenolic substances in young Danish men; 2009\u20132017","volume":"223","author":"Frederiksen","year":"2020","journal-title":"Int. J. Hyg. Environ. Health"}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/8\/4\/91\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:25:02Z","timestamp":1760178302000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/8\/4\/91"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,21]]},"references-count":31,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["toxics8040091"],"URL":"https:\/\/doi.org\/10.3390\/toxics8040091","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,21]]}}}