{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T16:12:16Z","timestamp":1775664736647,"version":"3.50.1"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T00:00:00Z","timestamp":1594857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"National Funds through FCT\u2014Foundation"},{"name":"Science and Technology within the scope of the project European Regional Development Fund","award":["PTDC\/DTP-FTO\/5651\/2014-POCI-01-0145-FEDER-016562"],"award-info":[{"award-number":["PTDC\/DTP-FTO\/5651\/2014-POCI-01-0145-FEDER-016562"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cannabis consumption is increasing worldwide either for recreational or medical purposes. Its use during gestation is associated with negative pregnancy outcomes such as, intrauterine growth restriction, preterm birth, low birth weight, and increased risk of miscarriage, though the underlying molecular mechanisms are unknown. Cannabis sativa main psychoactive compound, \u03949-tetrahydrocannabinol (THC) is highly lipophilic, and as such, readily crosses the placenta. Consequently, THC may alter normal placental development and function. Here, we hypothesize alterations of placental steroidogenesis caused by THC exposure. The impact on placental estrogenic signaling was examined by studying THC effects upon the enzyme involved in estrogens production, aromatase and on estrogen receptor \u03b1 (ER\u03b1), using placental explants, and the cytotrophoblast cell model BeWo. Aromatase expression was upregulated by THC, being this effect potentiated by estradiol. THC also increased ER\u03b1 expression. Actions on aromatase were ER\u03b1-mediated, as were abolished by the selective ER downregulator ICI-182780 and dependent on the cannabinoid receptor CB1 activation. Furthermore, the presence of the aromatase inhibitor Exemestane did not affect THC-induced increase in ER\u03b1 expression. However, THC effects on ER\u03b1 levels were reversed by the antagonists of CB1 and CB2 receptors AM281 and AM630, respectively. Thus, we demonstrate major alterations in estrogen signaling caused by THC, providing new insight on how cannabis consumption leads to negative pregnancy outcomes, likely through placental endocrine alterations. Data presented in this study, together with our recently reported evidence on THC disruption of placental endocannabinoid homeostasis, represent a step forward into a deeper comprehension of the puzzling actions of THC.<\/jats:p>","DOI":"10.1093\/toxsci\/kfaa110","type":"journal-article","created":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T11:09:24Z","timestamp":1593688164000},"page":"420-430","source":"Crossref","is-referenced-by-count":22,"title":["The Cannabinoid Delta-9-tetrahydrocannabinol Disrupts Estrogen Signaling in Human Placenta"],"prefix":"10.1093","volume":"177","author":[{"given":"Jo\u00e3o","family":"Maia","sequence":"first","affiliation":[{"name":"UCIBIO, REQUIMTE, Laborat\u00f3rio de Bioqu\u00edmica, Departamento de Ci\u00eancias Biol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Marta","family":"Almada","sequence":"additional","affiliation":[{"name":"UCIBIO, REQUIMTE, Laborat\u00f3rio de Bioqu\u00edmica, Departamento de Ci\u00eancias Biol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Lu\u00eds","family":"Mid\u00e3o","sequence":"additional","affiliation":[{"name":"UCIBIO, REQUIMTE, Laborat\u00f3rio de Bioqu\u00edmica, Departamento de Ci\u00eancias Biol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"Departamento de Qu\u00edmica, Universidade de Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Bruno M","family":"Fonseca","sequence":"additional","affiliation":[{"name":"UCIBIO, REQUIMTE, Laborat\u00f3rio de Bioqu\u00edmica, Departamento de Ci\u00eancias Biol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Jorge","family":"Braga","sequence":"additional","affiliation":[{"name":"Departamento da Mulher e da Medicina Reprodutiva, Servi\u00e7o de Obstetr\u00edcia, Centro Materno-Infantil do Norte-Centro Hospitalar do Porto, 4050-371 Porto, Portugal"}]},{"given":"Daniela","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Departamento da Mulher e da Medicina Reprodutiva, Servi\u00e7o de Obstetr\u00edcia, Centro Materno-Infantil do Norte-Centro Hospitalar do Porto, 4050-371 Porto, Portugal"}]},{"given":"Nat\u00e9rcia","family":"Teixeira","sequence":"additional","affiliation":[{"name":"UCIBIO, REQUIMTE, Laborat\u00f3rio de Bioqu\u00edmica, Departamento de Ci\u00eancias Biol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Georgina","family":"Correia-da-Silva","sequence":"additional","affiliation":[{"name":"UCIBIO, REQUIMTE, Laborat\u00f3rio de Bioqu\u00edmica, Departamento de Ci\u00eancias Biol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]}],"member":"286","published-online":{"date-parts":[[2020,7,16]]},"reference":[{"key":"2020101123043573800_kfaa110-B1","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1387\/ijdb.082758ea","article-title":"Estrogen regulation of placental angiogenesis and fetal ovarian development during primate pregnancy","volume":"54","author":"Albrecht","year":"2010","journal-title":"Int. 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