{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:22:42Z","timestamp":1785410562077,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,25]]},"group-title":"Pharmacology and Toxicology","reference-count":67,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["T32ES007148"],"award-info":[{"award-number":["T32ES007148"]}],"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01ES029275"],"award-info":[{"award-number":["R01ES029275"]}],"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30ES005022"],"award-info":[{"award-number":["P30ES005022"]}],"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01ES032144"],"award-info":[{"award-number":["R01ES032144"]}],"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R25ES020721"],"award-info":[{"award-number":["R25ES020721"]}],"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institute of Child Health and Human Development","award":["UC2HD113039"],"award-info":[{"award-number":["UC2HD113039"]}]},{"name":"National Institute of Child Health and Human Development","award":["UC2HD113039-02S1"],"award-info":[{"award-number":["UC2HD113039-02S1"]}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"crossref","award":["TL1TR003019"],"award-info":[{"award-number":["TL1TR003019"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Amnion Foundation"},{"name":"Dr. Gary and Mrs. Janis Grover Fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Rising global temperatures and eutrophication are increasing the intensity and frequency of cyanobacterial harmful algal blooms that release toxins including microcystin-LR (MC-LR). MC-LR inhibits protein phosphatases in the human liver and brain, but its accumulation in the placenta is unclear. Placental transporter expression varies across pregnancy and is influenced by physiological cues, such as low oxygen concentrations which activate HIF1A, and trophoblast cell fusion forming syncytiotrophoblasts that engage CREB-driven transcription. This study examined whether MC-LR accumulates in placental cells, which transporters mediate uptake, and how these transporters are regulated by HIF1A and CREB.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Intracellular accumulation of MC-LR (0.1\u201310 \u00b5M, 3 hour) was measured in human cytotrophoblasts (JAR, BeWo) and extravillous trophoblasts (HTR-8\/SVneo) by western blotting for MC-LR\u2013adducted proteins. Organic anion transporting polypeptide (OATP) involvement was tested using cyclosporin A (10 \u00b5M), an OATP inhibitor, before exposure to the OATP substrate or MC-LR. Cells were also cultured under 3%, 8%, or 20% O\u2082 to induce hypoxic responses or treated with forskolin (a potent intracellular cAMP inducer) to stimulate cell fusion before MC-LR exposure.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    MC-LR accumulated in all three placenta cell lines in a concentration-dependent manner. Cyclosporin A reduced MC-LR uptake by 57% in JAR cells, confirming OATP-mediated transport. Low O\n                    <jats:sub>2<\/jats:sub>\n                    increased OATP4A1 expression and function but reduced protein phosphatase expression, decreasing MC-LR\u2013bound proteins by 52\u201372%. Forskolin increased OATP4A1 expression and enhanced MC-LR uptake &gt;2.5-fold.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>MC-LR enters placental trophoblasts via active OATP transport, likely OATP4A1, and uptake increases under hypoxia and trophoblast fusion.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.22.713491","type":"posted-content","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T20:30:12Z","timestamp":1774470612000},"source":"Crossref","is-referenced-by-count":0,"title":["Transporter-Mediated Uptake of Microcystin-LR in Human Trophoblasts: Regulation By Oxygen Concentration and Cell Fusion"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0160-6648","authenticated-orcid":false,"given":"Michael Jeffrey","family":"Campbell","sequence":"first","affiliation":[{"name":"Rutgers University, Joint Graduate Program in Toxicology, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA"},{"name":"Rutgers University, Ernest Mario School of Pharmacy, Department of Pharmacology and Toxicology, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8522-267X","authenticated-orcid":false,"given":"Mokshitkumar","family":"Patel","sequence":"additional","affiliation":[{"name":"Rutgers University, Ernest Mario School of Pharmacy, Department of Pharmacology and Toxicology, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2027-9048","authenticated-orcid":false,"given":"Chenghui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Rutgers University, Joint Graduate Program in Toxicology, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA"},{"name":"Rutgers University, Ernest Mario School of Pharmacy, Department of Pharmacology and Toxicology, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8248-6849","authenticated-orcid":false,"given":"Xia","family":"Wen","sequence":"additional","affiliation":[{"name":"Rutgers University, Ernest Mario School of Pharmacy, Department of Pharmacology and Toxicology, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA"},{"name":"Environmental and Occupational Health Sciences Institute, 170 Frelinghuysen Rd, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7225-9132","authenticated-orcid":false,"given":"Shuo","family":"Xiao","sequence":"additional","affiliation":[{"name":"Rutgers University, Ernest Mario School of Pharmacy, Department of Pharmacology and Toxicology, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA"},{"name":"Environmental and Occupational Health Sciences Institute, 170 Frelinghuysen Rd, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0032-1037","authenticated-orcid":false,"given":"Lauren M.","family":"Aleksunes","sequence":"additional","affiliation":[{"name":"Rutgers University, Ernest Mario School of Pharmacy, Department of Pharmacology and Toxicology, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA"},{"name":"Environmental and Occupational Health Sciences Institute, 170 Frelinghuysen Rd, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"2","key":"2026032713001571000_2026.03.22.713491v1.1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3390\/toxins9020064","article-title":"Eutrophication and warming boost cyanobacterial biomass and microcystins","volume":"9","year":"2017","journal-title":"Toxins"},{"key":"2026032713001571000_2026.03.22.713491v1.2","doi-asserted-by":"crossref","unstructured":"Merder J , Harris T , Zhao G , Stasinopoulos DM , Rigby RA , Michalak AM . 2023. 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