{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T20:01:28Z","timestamp":1777406488598,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministero dell\u2019Universit\u00e0 e della Ricerca","award":["\u201cProgetti di Rilevante Interesse Nazionale\u201d (PRIN) 2017"],"award-info":[{"award-number":["\u201cProgetti di Rilevante Interesse Nazionale\u201d (PRIN) 2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Bisphenol A (BPA) is a ubiquitous, synthetic chemical proven to induce reproductive disorders in both men and women. The available studies investigated the effects of BPA on male and female steroidogenesis following long-term exposure to the compound at relatively high environmental concentrations. However, the impact of short-term exposure to BPA on reproduction is poorly studied. We evaluated if 8 and 24 h exposure to 1 nM and 1 \u00b5M BPA perturbs luteinizing hormone\/choriogonadotropin (LH\/hCG)-mediated signalling in two steroidogenic cell models, i.e., the mouse tumour Leydig cell line mLTC1, and human primary granulosa lutein cells (hGLC). Cell signalling studies were performed using a homogeneous time-resolved fluorescence (HTRF) assay and Western blotting, while gene expression analysis was carried out using real-time PCR. Immunostainings and an immunoassay were used for intracellular protein expression and steroidogenesis analyses, respectively. The presence of BPA leads to no significant changes in gonadotropin-induced cAMP accumulation, alongside phosphorylation of downstream molecules, such as ERK1\/2, CREB and p38 MAPK, in both the cell models. BPA did not impact STARD1, CYP11A1 and CYP19A1 gene expression in hGLC, nor Stard1 and Cyp17a1 expression in mLTC1 treated with LH\/hCG. Additionally, the StAR protein expression was unchanged upon exposure to BPA. Progesterone and oestradiol levels in the culture medium, measured by hGLC, as well as the testosterone and progesterone levels in the culture medium, measured by mLTC1, did not change in the presence of BPA combined with LH\/hCG. These data suggest that short-term exposure to environmental concentrations of BPA does not compromise the LH\/hCG-induced steroidogenic potential of either human granulosa or mouse Leydig cells.<\/jats:p>","DOI":"10.3390\/cells12111537","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T10:08:41Z","timestamp":1685700521000},"page":"1537","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Short-Term Exposure to Bisphenol A Does Not Impact Gonadal Cell Steroidogenesis In Vitro"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7702-3196","authenticated-orcid":false,"given":"Neena","family":"Roy","sequence":"first","affiliation":[{"name":"Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Lazzaretti","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elia","family":"Paradiso","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Capponi","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommaso","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Reggianini","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Sperduti","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy"},{"name":"Center for Genomic Research, University of Modena and Reggio Emilia, 42121 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lara","family":"Baschieri","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy"},{"name":"International PhD School in Clinical and Experimental Medicine (CEM), University of Modena and Reggio Emilia, 42121 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0972-4000","authenticated-orcid":false,"given":"Elisa","family":"Mascolo","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmela","family":"Perri","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Varani","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathological Anatomy, Azienda USL\/Azienda Ospedaliero-Universitaria of Modena, 41126 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Canu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathological Anatomy, Azienda USL\/Azienda Ospedaliero-Universitaria of Modena, 41126 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommaso","family":"Trenti","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathological Anatomy, Azienda USL\/Azienda Ospedaliero-Universitaria of Modena, 41126 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Nicoli","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Fertility Center, ASMN, Azienda Unit\u00e0 Sanitaria Locale-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daria","family":"Morini","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Fertility Center, ASMN, Azienda Unit\u00e0 Sanitaria Locale-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Iannotti","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Fertility Center, ASMN, Azienda Unit\u00e0 Sanitaria Locale-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Teresa","family":"Villani","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Fertility Center, ASMN, Azienda Unit\u00e0 Sanitaria Locale-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0399-0145","authenticated-orcid":false,"given":"Elena","family":"Vicini","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2133-4304","authenticated-orcid":false,"given":"Manuela","family":"Simoni","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy"},{"name":"Center for Genomic Research, University of Modena and Reggio Emilia, 42121 Modena, Italy"},{"name":"Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, 41125 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5571-392X","authenticated-orcid":false,"given":"Livio","family":"Casarini","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy"},{"name":"Center for Genomic Research, University of Modena and Reggio Emilia, 42121 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1289\/ehp.1307728","article-title":"Bisphenol A and reproductive health: Update of experimental and human evidence, 2007\u20132013","volume":"122","author":"Peretz","year":"2014","journal-title":"Environ. 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Issues"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1210\/endo.132.6.8504731","article-title":"Bisphenol-a: An estrogenic substance is released from polycarbonate flasks during autoclaving","volume":"132","author":"Krishnan","year":"1993","journal-title":"Endocrinology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"106563","DOI":"10.1016\/j.envint.2021.106563","article-title":"Human biomonitoring initiative (HBM4EU): Human biomonitoring guidance values (HBM-GVs) derived for bisphenol A","volume":"154","author":"Ougier","year":"2021","journal-title":"Environ. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1021\/es9028292","article-title":"Urinary bisphenol A concentrations in relation to serum thyroid and reproductive hormone levels in men from an infertility clinic","volume":"44","author":"Meeker","year":"2010","journal-title":"Environ. Sci. Technol."},{"key":"ref_9","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":"ref_10","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S1570-0232(02)00547-0","article-title":"Measurement of bisphenol A in human urine using liquid chromatography with multi-channel coulometric electrochemical detection","volume":"780","author":"Ouchi","year":"2002","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_11","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. 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