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Results showed that T\u20102 toxin strongly attenuated luteinizing hormone\/choriogonadotropin receptor (<jats:italic>LHCGR<\/jats:italic>) mRNA expression in follicle\u2010stimulating hormone (FSH)\u2010stimulated human cumulus granulosa cells. Addition of human chorionic gonadotropin was not able to elicit maximal response of ovulatory genes amphiregulin, epiregulin, and progesterone receptor. T\u20102 toxin reduced mRNA levels of <jats:italic>CYP19A1<\/jats:italic> and steroidogenic acute regulatory protein (<jats:italic>STAR<\/jats:italic>) and lowered FSH\u2010stimulated estradiol and progesterone production. Mechanistic experiments demonstrated that T\u20102 toxin decreased FSH\u2010stimulated cyclic adenosine monophosphate (cAMP) production. Addition of total PDE inhibitor 3\u2010isobutyl\u20101\u2010methylxanthine prevented T\u20102 toxin's action on <jats:italic>LHCGR<\/jats:italic>, <jats:italic>STAR<\/jats:italic>, and <jats:italic>CYP19A1<\/jats:italic> mRNA expression in FSH\u2010stimulated human cumulus granulosa cells. Furthermore, T\u20102 toxin partially decreased 8\u2010bromoadenosine 3\u20325\u2032\u2010cyclic monophosphate (8\u2010Br\u2010cAMP)\u2010stimulated <jats:italic>LHCGR<\/jats:italic> and <jats:italic>STAR<\/jats:italic>, but did not affect 8\u2010Br\u2010cAMP\u2010stimulated <jats:italic>CYP19A1<\/jats:italic> mRNA expression in human cumulus granulosa cells. Overall, our data indicate that environmentally relevant dose of T\u20102 toxin decreases steroidogenesis and ovulatory potency in human cumulus granulosa cells probably through activation of PDE, thus posing a significant risk for female fertility.<\/jats:p>","DOI":"10.1002\/tox.22752","type":"journal-article","created":{"date-parts":[[2019,4,6]],"date-time":"2019-04-06T09:17:36Z","timestamp":1554542256000},"page":"844-852","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["T\u20102 toxin downregulates <i>LHCGR<\/i> expression, steroidogenesis, and cAMP level in human cumulus granulosa cells"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9274-7723","authenticated-orcid":false,"given":"Kristina","family":"Pogrmic\u2010Majkic","sequence":"first","affiliation":[{"name":"University of Novi Sad Faculty of Sciences, Department of Biology and Ecology  Novi Sad 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