{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T02:48:09Z","timestamp":1783392489903,"version":"3.54.6"},"reference-count":93,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research","award":["PRIN to R. Pierantoni 2017"],"award-info":[{"award-number":["PRIN to R. Pierantoni 2017"]}]},{"name":"Universit\u00e0 degli Studi della Campania \u201cL. Vanvitelli\u201d","award":["VALERE, Vanvitelli per la Ricerca 2019 to G. Cobellis"],"award-info":[{"award-number":["VALERE, Vanvitelli per la Ricerca 2019 to G. Cobellis"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The objective of this work has been to characterize the estrogenic activity of bisphenol-A (BPA) and the adverse effects on the endocannabinoid system (ECS) in modulating germ cell progression. Male offspring exposed to BPA during the foetal-perinatal period at doses below the no-observed-adverse-effect-level were used to investigate the exposure effects in adulthood. Results showed that BPA accumulates specifically in epididymal fat rather than in abdominal fat and targets testicular expression of 3\u03b2-hydroxysteroid dehydrogenase and cytochrome P450 aromatase, thus promoting sustained increase of estrogens and a decrease of testosterone. The exposure to BPA affects the expression levels of some ECS components, namely type-1 (CB1) and type-2 cannabinoid (CB2) receptor and monoacylglycerol-lipase (MAGL). Furthermore, it affects the temporal progression of germ cells reported to be responsive to ECS and promotes epithelial germ cell exfoliation. In particular, it increases the germ cell content (i.e., spermatogonia while reducing spermatocytes and spermatids), accelerates progression of spermatocytes and spermatids, promotes epithelial detachment of round and condensed spermatids and interferes with expression of cell\u2013cell junction genes (i.e., zonula occcludens protein-1, vimentin and \u03b2-catenin). Altogether, our study provides evidence that early exposure to BPA produces in adulthood sustained and site-specific BPA accumulation in epididymal fat, becoming a risk factor for the reproductive endocrine pathways associated to ECS.<\/jats:p>","DOI":"10.3390\/ijms22052540","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T20:29:48Z","timestamp":1614803388000},"page":"2540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Characterization of Estrogenic Activity and Site-Specific Accumulation of Bisphenol-A in Epididymal Fat Pad: Interfering Effects on the Endocannabinoid System and Temporal Progression of Germ Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1720-1496","authenticated-orcid":false,"given":"Teresa","family":"Chioccarelli","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, Sez. Bottazzi, Universit\u00e0 degli Studi della Campania \u201cL. Vanvitelli\u201d, Via Costantinopoli 16, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Migliaccio","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sez. Bottazzi, Universit\u00e0 degli Studi della Campania \u201cL. Vanvitelli\u201d, Via Costantinopoli 16, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Suglia","sequence":"additional","affiliation":[{"name":"EHESP, Inserm, Irset (Institut de Recherche en Sant\u00e9, Environnement et Travail)\u2014UMR_S 1085, Universit\u00e9 de Rennes, 35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Manfrevola","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sez. Bottazzi, Universit\u00e0 degli Studi della Campania \u201cL. Vanvitelli\u201d, Via Costantinopoli 16, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Porreca","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sez. Bottazzi, Universit\u00e0 degli Studi della Campania \u201cL. Vanvitelli\u201d, Via Costantinopoli 16, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Diano","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sez. Bottazzi, Universit\u00e0 degli Studi della Campania \u201cL. Vanvitelli\u201d, Via Costantinopoli 16, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Errico","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sez. Bottazzi, Universit\u00e0 degli Studi della Campania \u201cL. Vanvitelli\u201d, Via Costantinopoli 16, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Fasano","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sez. Bottazzi, Universit\u00e0 degli Studi della Campania \u201cL. Vanvitelli\u201d, Via Costantinopoli 16, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5884-9208","authenticated-orcid":false,"given":"Gilda","family":"Cobellis","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sez. Bottazzi, Universit\u00e0 degli Studi della Campania \u201cL. 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